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Two selective breedings of mice for minimal or maximal agglutinin response to heterologous erythrocytes were carried out (selection I and II). Preliminary reported data indicated that for both selections the heritability was between 0.18 and 0.36 and the number of relevant loci from 7-13. The results reported in this article are definitive since the data of ten to twenty generations at selection limit are available and large populations of interline hybrids F1, F2 and both backcrosses were analysed. The character `high response' was partially dominant in F1 hybrids of both selections, the degree of this incomplete dominance was 0.27 in selection I and 0.54 in selection II. In selection I, 38% of the F2 variance was due to genetic factors (VG) and 62% to environmental effects (VE). The partition of phenotypic variance of F2 and back-crosses into additive variance (VA) and dominance variance (VD) was made according to three methods and the mean results were: VA = 0.72 and VD = 0.05. The resulting mean heritability was 0.35 and the number of relevant loci about ten. In selection II, 69% of the F2 variance was due to VG and 31% to VE. The three methods of variance calculation give somewhat discordant results. According to the more probable estimation (see discussion) VA = 0.95, the mean heritability was 0.23 and the number of loci, about 6. The results obtained in crosses between homologous lines of the two selections indicate that the two `high' lines have probably identical homogeneous genetic constitution while the two `low' lines contain some different `high' effect loci. [ABSTRACT FROM AUTHOR]

Outbred Swiss mice show a stable level of circulating thymic factor (TF) (measured by its action on theta-positive rosette-forming cells (RFC)) until the 6th month of life. Afterwards, this level progressively declines. Swiss mice genetically selected as 'high' and 'low' responders for anti-sheep red blood cell haemagglutinin production show no difference with ordinary Swiss mice with regard to serum TF level. This observation is compatible with previous results showing that the selection mainly induces changes in B-cell reactivity without T-cell modification. Conversely, genetic selection of Swiss mice based on spontaneous antinuclear autoantibody production (tested by immunofluorescence) induces a decrease in TF level, which has already become significant by 2 months of life. The mice thus selected (Swan mice) which present autoimmune manifestations and immune complex disease, like NZB and B/W mice, show the same premature cessation of TF as these other autoimmune mice. Such abnormality is compatible with the T-cell deficiency of NZB, B/W and Swan mice. [ABSTRACT FROM AUTHOR]

Primary and secondary antibody responses to f and s antigens of Salmonella typhimurium have been studied in H and L lines of mice genetically selected for primary response to sheep erythrocytes (SE) (Selection I). The range of interline separation obtained (non-specific effect of Selection I) was as large as for the selection antigen in the primary response to f antigen and slightly smaller in the primary response to s antigen. For these two antigens the interline difference was reduced after booster. The kinetics of responses were compared with those obtained in H and L lines of Selections III and IV carried out for secondary responses to f and s antigens of S. typhimurium respectively (specific effect of Selection III and IV). The genetic analysis was made in Selection I from the variances of individual agglutinin titres obtained in large groups of interline hybrids immunized with S. typhimurium. These calculations gave a reliable estimate of the effective number of independent loci regulating primary and secondary responses. The results demonstrated a major difference in the genetic control: a single locus regulated the secondary response to f antigen while six loci were involved in the control of the primary response. A similar difference was evident for s antigen. The primary response was likely to be under polygeniC regulation although the effective number of loci could not be calculated, while the secondary response was under monogenic control. [ABSTRACT FROM AUTHOR]

The aim of this study was the identification of the cell type in which genes selected for high or low response to SRBC express their functions. Spleen cells from high (H) and Iow (L) responder mice were immunized with SRBC in the Mishell and Dutton system. An antibody response of different magnitude was found in cultures of H and L spleen cells, the difference being at least as great as that observed in vivo. This finding under experimental conditions allowing the exclusion of any influence of the animal milieu during the immune response, suggests macrophages, B, and T lymphocytes as possible target cells of gene action. In vitro cell separation and recombination experiments in which spleen cells were immunized with SRBC, TNP-LPS, or TNP-HRBC indicate that the genetic differences between H and L responders brought about by selective breeding are expressed in lymphocytes to a greater extent than in macrophages. The role of histoincompatibility in the recombination experiments is unlikely but cannot be excluded. Among lymphocytes, B cells but not helper T cells were found more responsive in cultures of spleen cells from H than from L mice. [ABSTRACT FROM AUTHOR]

Mice genetically selected according to their capacity to produce antibodies (high and low responder lines) were infested with Trichinella spiralis. High responder mice produced much higher levels of IgE and γ1 serum antibodies than low responder mice. IgG and IgM antibodies were detected by immunodiffusion analysis or passive haemagglutination only in animals of the high responder line and in very low concentrations. The number of living larvae present in the muscles was very similar in the animals of both lines 30, 60 or 75 days after infestation. [ABSTRACT FROM AUTHOR]

Summary. The antibody forming cells from lymph nodes of guinea-pigs immunized with sheep red cells or dinitrophenyl bovine γ-globulin were studied by the `rosette' technique (immunocyto-adherence test). Pretreatment of the cells with antisera against guinea-pig total γ-globulin abolished their capacity to form `rosettes'. Pretreatment with antisera specific for γ1 γ2 or γM, produced an important inhibition of `rosette' formation, attaining in many cases more than 90 per cent. The sum of the percentage of inhibition obtained with anti-γ1 and anti-γ2 separately, added to more than 100 per cent in every case. These results are interpreted as indicating that the same cell is simultaneously synthesizing γ1 and γ2-globulins. The morphological study of the antibody-forming cells revealed the presence of small and large lymphocytes, blasts and plasmocytes, and a very small proportion of macrophages. [ABSTRACT FROM AUTHOR]

The number of antibody producing cells, i.e. rosette forming cells (RFC) has been studied in the spleen of mice injected intravenously with a full immunizing dose of sheep RBC. The spleen of a non-immunized mouse contains a background of about 70,000 RFC (normal RFC), which do not appear to be the ‘target cells’ for antigens of sheep RBC. Our findings suggest that the spleen of a mouse contains about 4000 ‘target cells’ which initiate the immune response to sheep RBC. In the primary response, the rise of RFC is exponential for about 96 hours with a doubling time of 13 hours involving seven to eight consecutive doubling periods. The peak value of RFC is 1.6 × 106 per spleen. In the secondary response, the doubling time of RFC is 6–7 hours. The exponential rise lasts 72 hours and includes nine to eleven doubling periods leading to a peak of 3.5 × 106 RFC/spleen. Adjuvant in the primary response leaves the doubling time of RFC unaltered but prolongs the exponential rise until the 120th hour leading to a peak of 6.3 × 106 RFC/spleen after ten doubling periods. The effects of priming and adjuvant are not fully additive. [ABSTRACT FROM AUTHOR]

A method has been described for quantitative measurement of the intensity of cutaneous delayed hypersensitive reactions in rats. This method is based on the measurement of the weight of skin infiltration at the site of cutaneous reaction. In vivo decomplementation of rats with antigen-antibody complexes or aggregated γ-globulin is accompanied by a decrease in delayed hypersensitivity responsiveness. When the level of serum complement is reduced by 90 per cent delayed hypersensitive reactions are completely suppressed. The results presented, although suggestive, do not provide a definite proof of the role of complement in the development of delayed hypersensitive reactions in the skin. [ABSTRACT FROM AUTHOR]

The phagocytosis of 51Cr or 131I-labelled suspensions of heat-killed Salmonella enteritidis by the R.E.S. has been studied in mice and the results compared with the kinetic laws which govern the clearance of stable colloid suspensions. Clearance of bacteria followed an exponential function for the first few minutes, during which about 60 per cent were phagocytosed. Thereafter, the rate of clearance became progressively slower. The maximum extraction by the liver and spleen was calculated as only 48 per cent. Previous administration of heparin slowed the initial clearance of all doses of bacteria exceeding 5×107 per 20 g. No inverse relationship between dose and rate of clearance could be shown in either heparinized or normal mice. The greatest proportion of bacteria (70-80 per cent) were taken up by the liver. Bacteria were phagocytosed in preference to carbon particles, but were taken up less readily than heat-denatured albumin (CA). Blood clearance was promoted greatly by previous injection of specific immune serum and slightly by normal guinea-pig serum. Further investigations suggest that apparent slowing in clearance is due to the fact that not all members of a bacterial population are equally susceptible to phagocytosis. [ABSTRACT FROM AUTHOR]

Summary. Guinea-pig anti-Salmonella typhimurium antibodies of the γ2 and γM classes were obtained free of each other, and their properties were studied quantitatively. Macroglobulin antibodies were found to be about twenty times more efficient than γ2 in agglutination and opsonic activity in vivo. The cytophilic activity of both classes of antibodies was the same. [ABSTRACT FROM AUTHOR]