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1. Wild house mice have been bred at 18°C, 25°C, (partly at 70% R.H. and partly at 85% R.H.), and 32°C. From their birth to the age of 90 days the mice were regularly weighed, and from the age of 15 days the length of body and tail was measured. The age for attainment of fecundity was recorded. 2. Among the nestlings, the mice at 32° are a little heavier than at the other two temperatures — later on the mice at 18° are significantly heavier and have significantly longer bodies than at the other two temperatures. Already at the age of 15 days, viz., before the thermoregulation becomes functional, the tails area significantly longer at 32° than at 18°. At the age of 60 to 90 days the tails at 32° are about 45% longer than at 18°. That a lengthening of the tail may be caused by other factors than a higher temperature, is indicated by the fact that of the mice grown up at 25° those kept at 85% R.H. have significantly longer tails than those kept at 70% R.H. The lengthening of the tails is due to a lengthening of the individual vertebra, the number remaining the same. No difference in age for attainment of fecundity or in fertility was demonstrable. Nor was it possible to show a significant difference in litter size at the three temperatures. [ABSTRACT FROM AUTHOR]

This paper describes a new method for the morphological study of individual antibody-forming cells (AFC) on cell smears of the quality of normal haematological preparations. The early AFC response to polymerized flagellin of S. adelaide was studied in vivo using C57BL mice, which have very low background levels of AFC and in vitro using dispersed spleen cell cultures from CBA mice. AFC, arising as a result of in vivo or in vitro stimulation were found to comprise a heterogeneous population, including basophilic mononuclear cells, lymphocytes of most sizes, immature blast cells and occasional plasma cells. The earliest AFC detected comprised a high percentage (28 per cent in vivo, 31 per cent in vitro) of small lymphocyte-like cells. Studies of the incorporation of [³H]thymidine showed that most AFC arose by proliferation but that a proportion of AFC, the small lymphocyte-like cells, arose by differentiation of precursor cells not involving cell division. The effects of antigen concentration on the kinetics of AFC were investigated in vitro. Subtolerogenic antigen doses caused a delayed and decreased AFC response. [ABSTRACT FROM AUTHOR]

The rates of synthesis and degradation of glucose-6-phosphate dehydrogenase in the liver of male C57BL mice are followed by a modified immunochemical method. Mice are given labeled amino acids for a predetermined period, and the labeled enzyme is isolated from liver homogenates with goat anti-enzyme, followed by rabbit anti-goat IgG serum. The precipitates are either counted directly or analyzed on acrylamide gels. The rate of glucose-6-phosphate dehydrogenase synthesis is found to be independent of the state of induction or repression of the animal. The synthesis of the enzyme constitutes 0.20-0.25% of the synthesis of all soluble liver proteins. This rate is maintained even during periods of most rapid formation or disappearance of enzyme activity. Quantitative immunoprecipitation shows that similar amounts of precipitable antigen are present in induced and non-induced liver homogenates. The results indicate that the large reversible increase in activity of glucose-6-phosphate dehydrogenase, observed when animals are transferred from a high-fat to a fatless diet, does not involve the synthesis of a new enzyme protein, and that mechanisms involving modulation of existing enzyme molecules ought to be considered for the adaptation of this enzyme in mouse liver.

The amino acid sequence of the cyanogen bromide fragments H1-H3 from the γ chain of the plasmacytoma immunoglobulin MOPC I73 is reported. It represents the first 104 amino acid residues of this heavy chain, thus covering the major part of the VH region. This sequence allowed deflation of a third subgroup of variability for the heavy chain pool, in common between mouse and human immunoglobuhns. [ABSTRACT FROM AUTHOR]

A method is described for the isolation of the fastest prealbumin fraction PA1 from mouse serum. This fraction appears to behave identically to the urinary prealbumin fraction in electro-phoretic migration, strain and sex dependency and in immunological reactions Molecular weight is determined by diffusion and sedimentation as well as by sedimentation- diffusion equilibrium. The apparent lower molecular weight of serum prealbumin is due to its contamination by polysaccharides extracted from starch gel in the course of its isolation. [ABSTRACT FROM AUTHOR]

Bone marrow-thymus cooperation experiments were carried out in lethally irradiated mice with sheep red blood cells (SRBC) as the antigen and direct plaque-forming cells (PFC) as the end point. Various parameters were altered, with the following results: (1) Above 800 rad, the response by marrow cells alone, as well as the increase due to added thymus cells, was independent of irradiation dose. (2) The response of marrow cells was greatest at high SRBC concentrations, but the co-operative effect of thymus cells was most evident at lower SRBC levels, and completely absent at high levels. (3) Increasing the number of marrow cells, without thymus, gave increasing numbers of PFC, but the dose-response curve did not suggest cell synergism. (4) Thymectomy and antithymocyte serum treatment of host or donor did not prevent the response by marrow cells alone. It was concluded that this was a true IgM response by antibody-forming precursors from the marrow, unaided by thymus-derived cells. [ABSTRACT FROM AUTHOR]

The immune response elicited by immunogenic forms of bovine γ-globulin (BGG), such as heat aggregated BGG (aBGG), BGG in Freund's incomplete adjuvant (FIA) or BGG plus endotoxin (ET), was interrupted by a single injection of cyclophosphamide. The amount of soluble BGG (sBGG) required to induce paralysis did not differ significantly between cyclophosphamide-treated mice and untreated mice. The injection of l mh sBGG together with 100 μg aBGG or 10 μg ET caused an immune response in normal mice but induced paralysis in cyclophosphamide-treated mice. However, without sBGG, the administration of aBGG suspension or aBGG in FIA could not induce paralysis, even with the aid of cyclophosphamide. [ABSTRACT FROM AUTHOR]

By using T cell-deprived mice and appropriate controls it has been shown that the adjuvant activity of LPS on the immune response to different doses of SRBC, tends to be oriented more towards B cells than towards T cells. In contrast, lentinan seems to mediate its adjuvant activity largely through a stimulatory effect on helper T cells. [ABSTRACT FROM AUTHOR]

The classes of immunoglobulin-containing cells in the lungs of mice after primary infection with Sendai virus were studied using an indirect immunofluorescence technique. It was found that during the first 5 days of the infection there was a considerable increase in all classes of immunoglobulin-containing cells with the IgA-containing cells retaining their pre-infection predominance. By the 6th day of the infection both IgG and IgA cells were present in equal numbers. This 1: 1 ratio persisted for nearly 30 days and was followed by a gradual reversion to IgA excess. IgM-containing cells represented only 1/15-1/30 of all immunoglobulin-containing cells at any time during the infection. [ABSTRACT FROM AUTHOR]

Injection of bovine serum albumin (BSA) with the capsular polysaccharide of Klebsiella pneumoniae (CPS-K) as adjuvant strongly primes mice for booster injections of BSA alone. The best doses of antigen for booster injections varied according to the frequency of antigen injections and the time interval between antigen injections. Increase in memory following the injection of BSA mixed with CPS-K adjuvant was first detected 10 days later. Memory continued to increase as the time interval after priming was increased to 90 days. Memory for the tertiary response increased after the optimum secondary antigenic stimulus. Increase in memory after the secondary antigenic stimulus was detected as early as 7 days after injection. Even secondary injection of the high dose of 50 mg of BSA did not exhaust immunological memory. Memory was also increased after the tertiary antigenic stimulus. Extremely high antibody responses (up to 492 mg protein per ml of antibody) could be obtained by eliciting tertiary and quaternary antibody responses optimally at the time memory was developed to the maximum level. [ABSTRACT FROM AUTHOR]

Recent experiments concerning the possible rule of components of the pituitary - adrenocortical axis (ACTH and glucocorticoids) in isolation-induced intermale fighting behavior in laboratory strains of mice are reviewed. A series of experiments which investigate factors that may influence the successful demonstration of this relationship are described. Differences in performances in standard-opponent tests of some outbred strains of albino mice are indicated, as well as an interesting positive correlation between the aggressiveness and the relative adtenal weights of the strains employed. Long-acting preparations of both ACTH and ACTH +10, injected throughout a period of isolation, suppressed fighting behavior in intact TO-strain mice in subsequent standard-opponent and trained-fighter tests. After it had been confirmed that vigorous isolation-induced fighting could be obtained in bilaterally castrated mice which had been subcutaneously implanted with testosterone pellets, the effects of long-acting preparations of ACTH, ACTH 4-10, ACTH 1-10, and ACTH 4-10 D-phe on the fighting behavior of such animals were studied. A significant suppression of fighting behavior was evident only with respect to ACTH, suggesting that ACTH 4-10 may have its action on this behavior in a manner rather different form that of the parent molecule. Some evidence was also obtained indicating that the zinc used in the preparation of long-acting injections of ACTH and its analogs may also cause a decline in the level of fighting behavior, in a standard-opponent test, in TO-strain mice which had been castrated and testosterone implanted. While such a finding does not affect the validity of the recorded behavioral influences of ACTH and ACTH 4-10 described earlier, it does seem likely that the presence of this substance In placebo injections would make the demonstration of the actions of the peptides difficult, as there would be a low level of fighting in all categories. [ABSTRACT FROM AUTHOR]

In the nucleus of L5178 Y cells, a lymphocytic mouse leukemia cell strain, newly synthesized 5-S ribosomal RNA first appears mainly in the nucleoplasm and then diffuses into the nucleotus. Kinetic studies have revealed that the appearance rates of 5-S RNA and ‘45-S fraction’ ribosomal precursor RNA are identical. During the first 30 rain, 5-S RNA binds to proteins and constitutes a nuclear pool of independent ribonucleoprotein particles which sediment at approximately 11 S. After this time, it begins to integrate with the nucleolar ‘80-S nascent’ particle. This ribonucleoprotein particle contains ‘45-S fraction’ RNA, the direct product of ribosomal DNA genes and has been shown to represent the first stage of ribosome formation. 5-S RNA remains associated to preribosomal particles during the nuclear maturation process leading to the large ribosomal subunit, located in the cytoplasm. In labeling experiments, the molar ratio of labeled 5-S RNA compared to high-molecular-weight ribosomal RNA in ribonucleoprotein particles, continues to increase until reaching a value of 1:1 for steady-state labeling. The association of 5-S RNA to preribosomal particles is more labile than it is to the mature ribosomal subunit. Chemical products such as heparin or sarkosyl used to extract nucleolar ribonucleoprotein particles, were shown to detach 5-S RNA from these particles; but dithiothreitol keeps the particles intact. [ABSTRACT FROM AUTHOR]

[5-3H]Uridine incorporation into ribosomes and other postribosomal ribonucleoprotein particles has been determined in mouse plasmocytoma MOPC406 cytoplasm after cell wall disruption. It has been shown that a large part of the radioactivity after 40 to 90-mm incubation is localized in the post- ribosomal zone of the gradient. The question arises whether these particles are the result of nuclear leakage during cell disintegration or whether they are native to the cytoplasm. To clarify this we have compared the following characteristics of cytoplasmic and nuclear ribonucleoprotein particles: (a) sensitivity to sodium deoxycholate; (b) sedimentation patterns in sucrose gradients; (c) buoyant density values in CsCl gradient; (d) dynamics of precursors incorporation into cytoplasmic ribonucleoprotein particles RNA. All these results have been considered as supporting the cytoplasmic origin of cytoplasmic post-ribosomal ribonucleoprotein particles. [ABSTRACT FROM AUTHOR]

Glucose-6-phosphate dehydrogenase is purified from C57BL mouse liver to a specific activity of 116 units/mg protein. The molecular weight of the main active unit is 121000 and it is composed of three interconvertible subforms as revealed by acrylamide electrophoresis. The main active unit is composed of two subunits of molecular weight 62000, and may aggregate to form higher oligomers. Amino acid composition and dependence of rate on pH and substrate concentration are reported. The kinetic data suggest the existence of two types of active sites with separate sets of Km and V values. The electrophoretic and kinetic properties of the enzyme from induced and non- induced liver homogenates are compared.

The activity of glucose-6-phosphate dehydrogenase in mouse liver is induced nearly 10-fold and the activity of citrate lyase nearly 6-fold, when C57BL mice are transferred from a diet containing 25% corn oil to a fatless diet. When the mice on the fatless diet are transferred back to the high-fat diet, both enzymes return to theft basal level with half-lives of 41 and 55 h, respectively. Malate-NADP dehydrogenase and 6-phosphogluconate dehydrogenase are induced and repressed in parallel, but to a lesser extent. In addition to the induction-repression cycle, all four enzymes also undergo diurnal variations involving 50% changes in their activities. Glucose-6-phosphate dehydrogenase is induced to a certain extent also in adipose tissue, but not in several other mouse tissues. The induction cycle can be repeated in liver at least three times successively. Glucose-6-phosphate dehydrogenase induction takes place in the bulk of parenehymal liver cells and not in a selected population. Actinomycin D and cycloheximide administration prevents the induction of the enzymes, but it is not clear whether a direct effect on the enzyme-synthesizing machinery is involved.

The disappearance of immunogenicity of human serum albumin (HSA) was measured by injection of 1 μg of this protein in normal mice and by transferring to them, at intervals, a fixed number of HSA-sensitized syngeneic spleen cells: sub-sequently the antigen binding capacity of the serum was determined. This system served to reveal the residual amount of immunogen present in the animal, since under these conditions the adoptive secondary response is proportional to the HSA available, and no antibody is formed by the host. The half-life of HSA immunogenicity was 17½ hours. A similar rate of decline (T = 16½ hours) was found by following 131I coupled to the HSA in the circulation of the same mice. This demonstrates that the albumin antigen is not stored in an active form in non-pre-immunized mice.

A novel type of immunosuppressive agent, 3-acetyl-5-(4-fluorobenzylidene) 4-hydroxy-2-oxo-2:5-dihydrothiophen (I.C.I. 47,776) inhibits the production of antibodies in rats when given orally. The treatment is still effective when commenced several days after immunization. No effect has been demontrated in mice or in guinea-pigs. [ABSTRACT FROM AUTHOR]

The functional activities of peritoneal cells in exudates of normal mice were studied. Antigen-containing peritoneal cells were tested for their ability to induce antibody by transfer into normal syngeneic recipients. Collection of peritoneal cells at varying time intervals following intraperitoneal injection of formalin-killed pneumococci or capsular polysaccharide, resulted in a decrease with time in the ability of these cells to induce antibody in the recipient mice. This finding could be ascribed to changes in the cell population in the peritoneum as a result of antigen administration rather than to loss of immunogenic material from these cells. Evidence for this comes from experiments in which peritoneal cells collected ½-hour after antigen administration were maintained in vitro for up to 24 hours. The immunogenicity of carbohydrate antigen in these cells persists for at least 24 hours. Furthermore our morphological observations showed a drop in macrophages following antigen administration. Our findings indicate that peritoneal exudates also contain immunocompetent cells. For this study we used recipient mice irradiated with 650–800 r, which completely suppressed their antibody response. Peritoneal cells collected 2 hours after injection of formalin-killed pneumococci led to serum antibody in the irradiated recipients 7 days later. By partially fractionating peritoneal cells on glass surfaces, it could be shown that the cells nota dhering to glass (lymphocytes and medium sized cells) were mainly responsible for this antibody response. Cells adhering to glass which contained most of the antigen-containing large macrophages and also medium sized cells, were much less effective in inducing antibody. In addition, peritoneal cells induced with thioglycollate medium consisting mainly of large macrophages and very few lymphocytes, actively induced antibody in normal recipients but failed to restore antibody production in the highly irradiated mice. The transfer of antibody formation to irradiated mice thus is due to immunocompetent cells in normal peritoneal exudates. [ABSTRACT FROM AUTHOR]

Mice given a single subcutaneous inoculation of highly-purified ovalbumin in water-in-oil emulsion yielded peak antibody titres which were about 500 times those stimulated by the same dose of ovalbumin without adjuvant, and which remained at the peak level for at least a year. Neither the oil, nor the emulsifier, nor the emulsion itself when injected at a separate site from the antigen, stimulated a response of this type. The response was not affected by a simultaneous subcutaneous injection of anti-ovalbumin, or by the later inoculation of a different antigen in water-in-oil emulsion, or by further inoculations of ovalbumin in saline. Ovalbumin was detectable in emulsion recovered from injected mice for up to 544 days after inoculation and its half-life within the emulsion was found to be about 90 days. The observations indicated that this type of adjuvant may exert its effect solely by the slow and even release of very tiny quantities of antigen over a long period of time. A mechanism by which such a release may take place is suggested. [ABSTRACT FROM AUTHOR]

The in vitro cytotoxic effect of spleen cells of mice immunized by tumour allografts was studied by measuring target cell inactivation as a function of release of radioactive label (51 Cr) or loss of cloning efficiency. When sensitized lymphoid cells were incubated with target cells at a ratio of 100: 1, up to 90 per cent of the incorporated label was released within 6–9 hours, while the number of clone- forming cells was reduced by up to 99 per cent in the same time period. Isoantiserum from the graft recipients, as well as its 1 9S and 7S fractions, protected target cells against the toxic effect of the spleen cells, but a lipoprotein antigen isolated from the tumour cells failed to inhibit the cytotoxic reaction. Target cell lysis as measured by specific release of 51Cr was partially inhibited by actinomycin-D and by cycloheximide at concentrations which effectively blocked DNA! dependent RNA and protein synthesis.

The role of haemolytic complement activity in the rejection of skin homografts in mice was studied. Two co-isogenic lines of mice were used, which are only known to differ in one respect. One line (B10.D2 new) possesses haemolytic complement activity, while the other line (B10.D2 old) lacks such activity. Both lines of mice rejected CF-1 and C57B1/6J skin grafts at essentially the same rate. It was therefore concluded that the presence or absence of haemolytic complement activity does not affect the rejection of skin homografts in mice. To determine if B10.D2 new and B10.D2 old line are histocompatible, skin grafts were exchanged between members of both lines. Although B10.D2 new line mice accepted B10.D2 old line skin grafts without exception, the reverse situation did not always obtain. The possible role of Hc, as well as alternative reasons for the observed histoincompatibility, are discussed. [ABSTRACT FROM AUTHOR]

The ability of C57BL, C3H, and A strain marrow cells to proliferate on transplantation into irradiated isogenic, F1 hybrid, and backcross progeny mice has been investigated by the spleen-colony technique and by measuring the newly-formed DNA in the recipient spleen with [131I] 5-iododeoxyuridine. Transplants of C57BL cells grew poorly in (A × C57BL) F1 and in (C57BL × C3H) F1 and reciprocal hybrids, as compared with isogenic and allogeneic hosts, whereas C3H and A strain marrow grafts were successful in isogenic, F1 hybrid and backcross recipients. In segregating backcross progeny, i.e. in offspring from F1 hybrid females mated to C57BL males, the frequency of success or failure of the C57BL grafts suggested that the trait was controlled by a single pair of genetic determinants at an autosomal locus. The latter is apparently linked with, or part of, the H-2 region in the IXth linkage group. The experimental evidence suggested also that the failure of C57BL haemopoietic cell grafts in H-2 heterozygotes was not related to exhaustion of donor cells by excess of recipient isoantigen but rather to lack of expression in the heterozygotes of histocompatibility-related growth requirements yet undefined. These requirements are specific for haemopoietic cells, but not for skin grafts, and resulted most probably from the effect of genetic (inter-allelic) interaction involving H-2 or an H-2-linked locus. [ABSTRACT FROM AUTHOR]

A survey of a number of rabbit antisera to Bordetella pertussis revealed the existence of two distinct antibodies, one passively protecting mice against lethal infection by the intracerebral route, the other passively protecting mice against lethal infection by the intranasal route. Neither is the antitoxin. Antisera against most, if not all, S forms of B. pertussis contain both types of protective antibody, and so to a lesser extent do B. parapertussis and B. bronchisepticus. Neither of the protective antigens is an agglutinogen, or the haemagglutinin. The two antigens can also be distinguished by active protection tests. Extensive investigations, however, had not led to an in vitro test for either of the protective antigens or their antibodies that would replace the mouse test. The practical importance of the two distinct antigens and their antibodies is shown by the fact that assay by the intranasal and intracerebral routes of challenge will not arrange vaccines in the same order of potency either in active or in passive protection tests. [ABSTRACT FROM AUTHOR]

We cannot say that the intracerebral route or the intranasal route is a satisfactory method of determining the virulence of Bordetella pertussis for mice, but only that the intracerebral route determines the intracerebral virulence and the intranasal route the intranasal virulence, for these do not run hand in hand. Toxin plays a part in the intranasal virulence by facilitating the primary lodgement of the organism in the lung, probably by paralysing the cilia of the ciliated epithelium. Toxin does not appear to play any obvious role in intracerebral virulence in which primary lodgement is mechanical. The ability of the organism to grow in the tissue then comes into play. The factor responsible for growth in the lung does not appear to be identical with the factor responsible for growth in the brain. [ABSTRACT FROM AUTHOR]

ADRENAL cortical grafts transplanted between members of an inbred strain of mice (`isogralts') are held to be successful when they empower adrenalectomized mice to subsist upon a diet low in NaCl. By this criterion, in which due allowance must be made for the hypertrophy of accessory adrenal tissue, the intramuscular implantation of adrenal cortical shavings, free from medullary tissue, is a reliable method of grafting. The intravascular injection of dissociated cortical cells, though sometimes successful, is not reliable. The testis, the anterior chamber of the eye, and the brain will also serve as sites of transplantation, though less efficiently than muscle. Adrenal cortical grafts transplanted by the intramuscular method between members of different inbred strains of mice (`homografts') are unsuccessful. Homografts may, however, survive in the anterior chamber of the eye. Immunological tolerance may be procured in respect of adrenal cortical tissue: adult A-line mice into which CBA splenic cells have been injected shortly after birth will accept CBA adrenal homografts as readily as they accept isografts. It is accordingly argued that all the `transplantation antigens' possessed by a mouse's adrenal cortical tissue are also possessed by its spleen. Tolerant A-line mice subsisting upon homografts of CBA adrenal cortical tissue will die after adoptive immunization, i.e. after the injection of lymphoid cells taken from normal A-line mice which have been actively immunized against CBA tissues. It is shown that this procedure causes CBA tissue in the tolerant host to be destroyed; death is therefore attributed to an immunological `adrenalectomy'. Adrenal homografts transplanted between mice of unrelated strains behave essentially like skin homografts. No opinion is expressed upon whether or not adrenal homografts might survive their transplantation between mice belonging to strains which, though closely related, stand far enough apart for skin homografts to fail. [ABSTRACT FROM AUTHOR]

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A cross of eight inbred lines of albino mice was made in order to construct a heterogeneous sample representative of the laboratory species. An experiment incorporating the factors of light, noise, arena size, sex and days was performed using an open-field test standardized on the rat. The results obtained were compared with previous findings on inbred lines and F1s. Ambulation was markedly affected by most independent variables, whilst defaecation seemed less sensitive in relation to them. The utility of multiple crosses of inbred lines is discussed. [ABSTRACT FROM AUTHOR]

Within the limits of these experiments there appeared to be a difference in quality of the immune response of mice to Bovine Serum Albumin and Horse Ferritin. A primary injection of Bovine Serum Albumin in the mandibular labial sulcus was followed by cell replication and plasma cell differentiation in the cervical lymph nodes and a rise in serum antibody. No similar quantitatively measurable cellular response was found in the cervical lymph nodes to a primary injection of Horse Ferritin in the same site, although detectable quantities of serum antibody were present in the same animals. [ABSTRACT FROM AUTHOR]

Investigates whether unilateral dominance is not related to neuropsychological integrity in children. Absence of strong linear predictive relationships between LA and SLP; Limited significance of LA and SLP for human behavior.

The carrier specificity of secondary anti-hapten responses using different haptenic densities on autologous or heterologous carrier proteins was studied. In addition, the T cell requirements for anti-hapten antibody synthesis were investigated. The results demonstrated a clearcut decrease in carrier specificity as hapten density goes up. Also. memory against autologous hapten carrier conjugates at the T cell level waned with time in contrast to the memory against heterologous hapten-carrier conjugates. Specific helper cells against autologous conjugates were demonstrated by filtration through anti-immune-globulin coated columns. [ABSTRACT FROM AUTHOR]

Cryostat sections of mouse spleen and lymph nodes adsorbed sheep erythrocytes coated with rabbit or mouse lgG antibody. The reaction was mediated by the Fe part of the immunoglobulin molecule. Haemadsorption was inhibited by mouse IgG and antigen-antibody complexes. Complement was not required. Sensitized erythrocytes failed to bind to thymus and to the thymus dependent areas of the peripheral lymphoid tissue. Results of inhibition experiments with rabbit anti-mouse lymphocyte serum and anti-(-) serum further suggested that binding of sensitized crythrocytes to lymphoid tissue sections can be used as a marker for B lymphocytes. [ABSTRACT FROM AUTHOR]

The effect of 55 mg of cortisone acetate given to adult mice 1 day prior to the injection of 4 x 108 sheep erythrocytes was studied. This drug is able to suppress more than 95 per cent of splenic plaque-forming cells (PFC) compared with immunized animals not treated with cortisone. However, the anti-sheep red cell haemolytic titre in the blood was not affected. Several hypotheses to explain this paradox were tested experimentally. Plaque-forming cells in the bone-marrow of cortisone-treated mice, instead of being suppressed, increased to more than ten times their number compared with the controlled animals. [ABSTRACT FROM AUTHOR]

The effect of a single batch of horse anti-mouse thymocyte globulin on the humoral immune response has been extensively investigated in 10-12-weekold male mice of six inbred strains. The preparation under test readily suppressed the primary immune response of A/HeJ, C57B1, DBA/1, CBA and C3H mice to 0.1, 1.0 and 10.0 mg doses of alum precipitated bovine serum albumin (alum BSA). However, at the doses used it generally failed to significantly suppress the primary immune response of BALB/c mice to 0.1 and 1.0 mg doses of this antigen. Furthermore, the effectiveness of the suppression was somewhat diminished by the incorporation of bordetella pertussis organisms into the alum BSA inoculum. The product also suppressed the secondary immune response to alum BSA in C3H mice and C57B1 mice but, at the same doses, was without significant effect on the secondary responses of A/HeJ and CBA mice. [ABSTRACT FROM AUTHOR]

The time of appearance and counts of antigen-binding cells, using radioiodine-labelled flagellin and hemocyanin, was studied in the human and mouse foetus at different gestational ages: the capacity for binding radioiodinelabelled antigens was equated with acquisition of immunological function. Cells resembling lymphocytes from human and mouse liver and bone marrow showed antigen binding at early gestational ages, but tiffs binding could not be prevented with species-specific antisera to immunoglobulins. Specific antigen binding to lymphocytes was detected first with thymic lymphocytes, at gestational ages of 12 weeks in humans and 14 days in mice, then with splenic lymphocytes, at 16 weeks in humans and 17 days in mice, and still later with gut lymphocytes. Relative counts of antigen-binding cells in human foetal thymus were maximal at 16-22 weeks and decreased thereafter. Lymphocyte immunocompetence, as judged by the capacity specifically to bind antigen, develops rapidly after the appearance in thymus of cells with the morphology of lymphocytes; this seemed to occur at the equivalent foetal stage in the species studied. [ABSTRACT FROM AUTHOR]

The induction and loss of tolerance to native and depolymerized fractions of levan, a thymus-independent antigen, have been studied in (DBA/1 × CBA-T6T6)F1 mice by a direct plaque-forming cell (PFC) assay. Tolerance following 1 mg native levan began to break by 80 days, whereas mice remained specifically unresponsive 150 days after 10 mg. Effects attributable to long persistence of antigen have been demonstrated. The following main features of levan tolerance were established by transfer of spleen cells to 900 R-irradiated recipients: (1) the induction period is very short—less than 24 hours. (2) No detectable immunity accompanies or precedes induction. (3) The fall in immunogenicity with reduction in molecular weight (mol. wt) of levan is not accompanied by loss of tolerogenicity. An effectively tolerogenic, non-immunogenic fraction (mol. wt< 10,000) was found. (4) There is no rapid loss of tolerance following cell transfer (reactivity is only regained after 50 days), arguing against the existence of tolerant cells in this model. As these results and those from corresponding investigations with SIII and HGG all show major dissimilarities, it is considered imprudent to base generalizations concerning the nature of B cell tolerance on studies with only one type of antigen. Whether or not two different kinds of specific unresponsiveness might be implicated with these cells is discussed. [ABSTRACT FROM AUTHOR]

The immunological response to native levan (a fructose homopolymer with molecular weight 2 × 107) has been studied in (DBA/1 × CBA-T6T6)F1 mice by passive hemagglutination and plaque-forming cell (PFC) assays. It resembles type-specific pneumococcal polysaccharide (SSS) in eliciting a prolonged humoral antibody response over a wide dose range (0.0001-100 µg) and in inducing longlasting 'high zone' tolerance with a single injection (1 mg or more). Other similarities include an exclusively IgM response, independence of synergy with thymusderived lymphocytes and absence of immunological memory. On the other hand, parallelism between serum hemagglutinin and PFC levels following all doses of antigen implies that higher immunizing doses of levan, unlike SSS, do not engage in peripheral neutralization of antibody. It was concluded from studying the fate of 14C-labelled levan that this was attributable to more rapid elimination from the circulation and subsequent slow metabolism of this polysaccharide. Levan also differs from SSS in inducing tolerance directly, without a detectable prior immune phase. [ABSTRACT FROM AUTHOR]

Incorporation of [³H]thymidine into the spleens of intact mice during the primary and secondary responses to SRC has been studied. In both responses, auto-radiographs show a well marked increased incorporation of [³H]thymidine by cells in the peri-arteholar zone during days 1 and 2. The degree of labelling indicated that many of these cells were in S phase in preparation for mitosis. A similar response occurred in cells situated in the mantle layer on day 3 to day 4 of the primary response, but was much less evident in the secondary response. This was in keeping with the results of scintillation counting which showed that increased uptake of [³H]thymidine was more sustained in the primary than in the secondary response to SRC. Many lightly labelled cells indicating metabolic turnover of DNA developed in the red pulp of the spleen at times which coincided with the maximum development of antibody-producing cells (PFC) which occurred about 24 hours earlier in the secondary than in the primary response. Germinal centres showed many lightly labelled nuclei. In both primary and secondary responses these areas enlarged, becoming maximal in size after the peaks of PFC were achieved. It was concluded that the enlargement of germinal centres was the result of trapping of cells in the areas rather than proliferation. From these studies it appears that metabolic turnover of DNA occurred in areas of the spleen intimately associated with antibody formation. The possible role of this process in antibody synthesis is discussed in the light of these observations. [ABSTRACT FROM AUTHOR]

We have investigated the cell populations required for the in vivo and in vitro immune response of mouse spleen cells to rabbit Fab'2 and Fab' and sheep red blood cells (SRBC). The production of IgM antibodies to SRBC both in vivo and in vitro is dependent upon the presence of thymus-derived lymphocytes, although some response does occur in their absence. The IgG response can only be obtained in vivo, and is also dependent upon the presence of thymus-derived lymphocytes. By contrast, the in vivo and in vitro IgM response of mice to rabbit Fab'2 and Fab' is independent of the presence of thymus-derived lymphocytes, but the in vivo IgG response is thymus dependent. The in vitro response to both SRBC and rabbit Fab'2 is low in cultures depleted of macrophages, but the rabbit Fab'2 response appears less affected by macrophage depletion than the SRBC response. [ABSTRACT FROM AUTHOR]

An analysis was made of the antibody response in the spleen and lymph nodes of mice to erythrocyte antigens injected under conditions which have been reported to cause antigenic competition. In the spleen, injection of a different erythrocyte antigen 2-4 days before the injection of a test antigen had little or no effect on the total number of cells or the number of plaque-forming cells (PFC) to the test antigen. Examination of the antibody response in opposite lymph nodes of a mouse made possible a comparison between two different conditions of antigen exposure within the same individual. In the lymph nodes, preceding the injection of the test antigen by an injection of a different erythrocyte antigen 2-4 days earlier led not to a decrease, but, on the contrary, to an increase in the number of plaque forming cells to the test antigen. A similar increase in the number of plaque-forming cells per lymph node was observed for each of two test antigens, when these had been mixed and injected into the forefeet 24 hours after the injection of a different erythrocyte antigen. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to compare and contrast the migratory behaviour of three sub-classes of spleen lymphocytes in the mouse: cells capable of adsorbing a specific labelled antigen on to their surfaces ('antigenbinding' cells); bone-marrow-derived ('B') cells; and thymus-derived ('T') cells. Antigen-binding spleen cells were labelled in vitro with 125l-polymerized flagellin from Salmonella adelaide and injected intravenously into syngeneic recipients. Their distribution within the spleen was studied by radioautography for 24 hours after injection. Nearly all the antigen-binding cells localized and accumulated in and around the germinal centres of the white pulp. Bone-marrow-derived B-spleen cells which were labelled in vitro with ³H-uridine were found to localize in and around germinal centres. The proportion of B cells found in these regions was lower than the proportion of antigen-binding cells and there was not a progressive aggrregation of B cells over 48 hours. Thymus-derived T-spleen cells also labelled in vitro with ³H-uridine were located predominantly in the established thymus-dependent periarteriolar regions of the white pulp. The significance of the localization of antigen-binding cells in the germinal centre regions of spleen is discussed in relation to the B and T components of the spleen lymphocyte population. The conclusion was reached that B lymphoytes activated by contact with antigen Iodged preferentially in germinal centre areas. [ABSTRACT FROM AUTHOR]

Normal mouse spleen cells were stimulated in culture by phytohaemagglutinin (PHA), pokeweed mitogen (PWM), allogeneic cells; keyhole limpet haemocyanin (KLH) sensitized cells by the specific antigen. The stimulation of the cells was measured by [³H]thymidine incorporation into the TCA precipitable fraction of the cultures. In this systems the effect of treating the cells with an antibody against the theta antigen and aa antibody against immunoglobulin, with or without complement, was investigated. Treatment of the cells with antisera and complement or without complement gave similar results. The secondary in vitro stimulation with soluble antigen KLH could be markedly reduced with both anti-θ and anti-immunoglobulin serum. The response to alIogeneic cells in the mixed lymphocyte reaction was only reduced by anti-θ serum and not by antiimmumoglobulin serum. No definite effect could be demonstrated by either antibody on the non-specific stimulation by PHA or PWM. [ABSTRACT FROM AUTHOR]

The primary antibody response of the IgM type against sheep red blood cells, by spleen cells obtained from mice immunized in vivo has been studied at the cellular level. The modified plaque assay technique which was used allows the quantitative recording of plaque formation and growth in a carboxymethylcellulose gel. The distribution of plaque size at different times of incubation indicates that the secretion rate and the final amount of antibody released differ considerably between individual PFC of the same splenic population. However, the mean sizes of plaques from splenic populations at the same time after immunization are similar from mouse to mouse. During in vitro incubation, the kinetics of plaque growth display characteristic features, thus differentiating PFC populations from mice examined at different times after in vivo immunization. Most notably, there is a decrease in the mean size of the plaques between day 4 and day 5 following immunization. These results are discussed in terms of antibody secretion by PFC populations during the primary response. [ABSTRACT FROM AUTHOR]

In the antibody response to rabbit IgG in BALB/c mice, antigenic competition has been demonstrated between Fc and Fab'. Similar competition was found when a mixture of Fc and Fab' was used as antigen. In both cases the presence of Fc suppressed the antibody response to Fab'. Competition was demonstrable only in the primary antibody response. The effect on competition of varying the mutes and the time course of administration of the antigens was investigated. [ABSTRACT FROM AUTHOR]

Antilymphocytic globulin (ALG) suppressed the development of haemolytic anaemia with positive antiglobulin (Coombs) reactions in intact and adult thymectomized New Zealand Black (NZB) mice, although some recipients eventually became positive after treatment was stopped. Macroglobulinaemia and lymphoid cell infiltrates were resistant and complex nephritis was unaffected by, and in thymectomized recipients accelerated by, ALG, whilst many such recipients developed severe Coombs negative haemolytic anaemia. Splenomegaly was less pronounced in ALG treated than in control NZB mice. However, lymphoproliferative changes in general, and reticulum cell hyperplasia in particular, progressed despite ALG treatment in early life. On the other hand, this agent did not provoke overt neoplasia in the lymphatic or other tissues. Syngeneic lymphoid cells from young donors did not influence the disease of ALG treated mice but rat lymphoid cells in thymectomized recipients induced a temporary suppression of macroglobulinaemia and reticulum cell proliferation was reduced. [ABSTRACT FROM AUTHOR]

Characteristic lesions formed by mouse complement were visible in electron micrographs of Escherichia coli cell walls treated with aminoethylisothiouronium bromide and then incubated with normal mouse serum in vitro. However, lesions could not be detected in E. coli cell walls recovered from the blood of normal mice after intravenous injection. Lesions were not produced by either heated or complement deficient mouse sera in any of the experiments. After incubation with normal or complement deficient mouse serum E. coli cell walls were surrounded by a layer probably made up of complement components and immunoglobulins. This layer was less evident when the sera had been heated at 56° for 1 hour. Numerous lesions formed by the in vivo action of guinea-pig complement were found in E. coli cell walls recovered from the animal after intravenous injection. [ABSTRACT FROM AUTHOR]

To study the mechanism of antigenic stimulation in the secondary immune response, primed lymphoid cells were stimulated with antigen in various ways in vitro. The effect of antigenic stimulation was assessed by the antibody titres obtained after in vivo culture of palmed cells in X-irradiated recipients. Primed cells were much more effectively stimulated by antigen-antibody (Ag-Ab) complex than by free antigen. Primed cells could also be stimulated by spleen or lymph node cells from normal mice which had been exposed to free antigen or Ag-Ab complex in vitro or in vivo and thoroughly washed. Under these conditions, Ag-Ab complex was again much more effective than free antigen. When the cells were incubated with Ag-Ab complex, the dose of antigen bound to the cells was somewhat increased. But this increased binding of antigen could not solely account for the increase in immunogenicity. It is suggested that the ingestion of antigen by macrophages is facilitated by the presence of antibody and that the macrophages mediate the effective immune stimulus to memory cells. The effect of antibody in increasing the immunogenicity of antigen was lost completely when antibody was digested with pepsin. Thus, the Fc portion of antibody seemed to be important for this effect. However, it was demonstrated that antibody does not operate by becoming attached to macrophages as cytophilic antibody, and that complement is not involved in this process. The augmenting mechanism of antibody on the antigenic stimulation mediated by macrophages was discussed. [ABSTRACT FROM AUTHOR]

Immunofluorescent staining has been used to detect antigenic determinants on the surface of living lymphoid cells of mice. It has been possible to distinguish two distinct populations of peripheral lymphocytes: one population carries the theta isoantigen and is thymus-dependent; the other has naturally-occurring immunoglobulin determinants on the cell surface and appears to be thymus-independent. The relative proportions of these two populations of cells is characteristic for each type of lymphoid tissue and these proportions have been determined for thymus, lymph node, spleen, and thoracic duct cells. [ABSTRACT FROM AUTHOR]

The nature of two distinct anti-pneumococcal antibodies of mice has been further investigated. These antibodies, produced after the injection of purified SIII (the capsular polysaccharide of Diplococcus pneumoniae Type III), were examined for their serological properties in vitro and for their protective potency in vivo. The first anti-SIII antibody, distinguished by its ability to agglutinate antigen-coated erythrocytes, was not only unable to lyse these erythrocytes (with complement), but it protected them against lysis by the other antibody, because of its high affinity for the antigen. This haemagglutinating antibody did not precipitate soluble antigen, was of the IgA class, and could protect mice against challenge with virulent pneumococci. It was produced by mice given small doses (0.1 µg) of SIII, but not by mice given 50 µg. These latter were susceptible to pneumococcal challenge. The second antibody, which was haemolytic and precipitating but not haemagglutinating, had a comparatively low affinity for the antigen: thus it was not detectable when mixed with the first antibody, especially if the test erythrocytes were inadequately sensitized. This haemolytic antibody was of the IgM class. It was found in high titre in mice given 50 µg of SIII, but did not protect them against challenge. [ABSTRACT FROM AUTHOR]

Two series of experiments are described in which elimination of [131I]BGG is observed in CBA mice treated with mycobacterial adjuvants. Neither mycobacteria in oil nor Wax D in oil induced immune-type elimination in the first series where control mice catabolized the antigen relatively slowly (mean half-lives of 4.38 and 5.0 days). In a second series where control mice showed faster catabolism (mean half-lives 3.82 and 2.96 days) the adjuvants did induce immune elimination. It was found also that such adjuvants invariably accelerated the elimination rate in the pre-immune period of elimination. Porton White mice eliminated the antigen rapidly and even mice not given adjuvant frequently gave a secondary immune response on a further exposure to antigen. The results suggest that increases in the rate of antigen catabolism contribute to adjuvant activity in this model. [ABSTRACT FROM AUTHOR]

Germ-free CFW mice reared on practical type steam sterilized solid diets showed lower than conventional levels of all serum immunoglobulins. Reared on water soluble, low molecular weight, chemically defined diets which had been sterilized by filtration, young adult germ-free mice demonstrated almost total absence of immune globulins. However, in older animals reared on this diet, a gradual increase with age, notably of IgG, became apparent. Total white blood cell count and differential counts were only slightly and not significantly lower in germ-free mice fed solid diet than in their conventional controls. Germ-free mice fed the water soluble diet, on the other hand, showed substantially lower white cell counts than the animals reared on solid diet. It is concluded that steam sterilized solid diet constitutes a major source of uncontrolled exogenous stimulation of the lymphoid tissues. [ABSTRACT FROM AUTHOR]