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The delayed-type hypersensitivity (DTH) response in BALB/c mice to the idiotype of M315 (α, λ2), a BALB/c myeloma protein, can be suppressed by a single i.v. injection of soluble M315. This suppression involves the generation of suppressor T cells. Mice tolerized by M315 produce subcellular factors that suppress the M315-DTH response. Such suppressor factors can be obtained by mechanical disruption of spleen cells or thymocytes from mice treated i.v. with M315. The fine specificity of the factor was studied using various immunoadsorbents such as L315 and germline Vλ2 chain-Sepharose beads with known amino acid sequences. The results indicated that the specificity of the factor depended on three contiguous somatically mutated amino acid residues, Phe94, Arg95 and Asn96, in the third hypervariable region of the V domain of the L chain of M315. [ABSTRACT FROM AUTHOR]

The IgG2b, monoclonal antibody M10/76, which is specific for the Hooded rat fibrosarcoma MC24, was obtained by fusion of the rat myeloma Y3 Ag 1.2.3 with spleen cells from an MC24 tumour-bearing rat. This antibody has been found to inhibit lung colonization when MC24 cells were injected i.v. into Hooded rats, and when passively transferred into athymic MC24 tumour bearers, it prevented or considerably reduced the incidence of spontaneous lung metastases in more than half the treated animals. [ABSTRACT FROM AUTHOR]

The susceptibility to lysis by antibodies (Ab) and complement (C) of several murine myeloma tumour sublines was studied. Significant differences in the degree of C-mediated lysis were observed and found to be independent of the expression of antigens on the cell surface and their accessibility to react with Ab. Several experiments correlate the presence and amount of a 160 kilo dalton cell-surface glycoprotein (gp160) and the diminished susceptibility to C attack observed with some of these tumour sublines. Different sources of Ab and C were tested and similar results were obtained, although the effect was most apparent when mouse Al, and rabbit C were used in the cytotoxicity assays. These results suggest that gp160, when present in large amounts on the cell surface, could be interfering with the generation of the C-induced membrane lesions. [ABSTRACT FROM AUTHOR]

Rabbits were immunized with purified antidextran containing IgG2. Half of the animals were treated with commercial human IgG intravenously to induce colerance. The antisera were absorbed and/or eluted from IgG-Sepharose columns and the antibodies tested with a panel of at least eight human myeloma proteins of the four IgG subclasses, both kappa and lambda types. All animals produced mainly anti-IgG2 or IgG4, sometimes interchanged between these maxima or between kappa and lambda types over a series of bleedings. Absorption with IgG2 and/or IgG4 myeloma proteins resulted in sera or antibody preparations specific for the IgG1 or IgG3 subclasses, and the amount of those antibodies also varied between bleedings from the same animal. It may be concluded that anti-IgG2 and anti-IgG4 syntheses are related in a complementary manner or are equally likely to be produced in a response to IgG2; while IgG1 and IgG3 are also interrelated, but with an inverse relationship to IgG2 and IgG4. Alternatively anti-IgG2 and anti-IgG4 antibodies could be highly cross-reactive, and so could anti-IgG1 and anti-IgG3 antibodies. [ABSTRACT FROM AUTHOR]

An antigenic heterogeneity among IgD myeloma proteins was tested by immunoelectrophoresis and double immunodiffusion in agar with four kinds of anti-delta(Fc) antisera produced by immunization with isolated Fc fragments of IgD myeloma proteins. According to antigenicity of the Fc fragment, lgD myeloma proteins were divided into two different groups. Anti-delta(Fc)-Tl (S.T.) antiserum, absorbed with the Y.S. myeloma protein or serum, either gave a faint precipitin line or failed to react against the isolated IgD myeloma proteins or sera. With the papain-digested lgD mycloma proteins and sera, anti-del-ta(Fc)-T1 antiserum either gave heavy precipitin lines or failed to react. Of twelve papain-digested sera containing lgD myeloma proteins tested, nine (75%) showed positive precipitin lines using anti-delta(Fc)-T1 antiserum. No relationship was found between the two groups of myeloma proteins with respect to IgD levels. SDS polyacrylamide gel electrophoresis of the IgD myeloma proteins (S.T. and Y.S.) showed no difference in the molecular weights of the whole myeloma proteins, and their light and heavy chains. Polyacrylamide gel electrophoresis of the lgD myeloma proteins (ST. and Y.SJ, after treatment with papain, revealed almost the same patterns. [ABSTRACT FROM AUTHOR]

Polymeric and monomeric human IgA were isolated from the sera of patients with IgA myeloma; rat IgA polymer, monomer and 1gG2 were isolated from the ascitic fluid or sera of Lou/Wsl rats bearing appropriate myelomata. The purified Ig preparations were labelled with 125I and injected intravenously into rats, rabbits, guinea-pigs or sheep that had had a cannula inserted into the common bile duct so that their bile could be collected quantitatively. Rats and rabbits transported 30% of the injected dose of both IgA polymers, but no other type of immunoglobulin, from blood to bile within 5-1 h. Sheep and guinea-pigs were unable to transport any of the immunoglobulin preparations from blood to bile, even though the injected material remained circulating in the blood. Lemaître-Coelho, Vaerman, Bazin & Beckers, 1978) by the hepatocytes (Birbeck, Cartwright, Hall, Orlans & Peppard, 1979). Like enterocytes, the hepatocytes have SC on their surfaces and apparently transport IgA in much the same way (Orlans, Peppard, Fry, Hinton & Mullock, 1979; Socken, Jeejeebhoy, Bazin & Underdown, 1979; Mullock, Hinton, Dobrota, Peppaul & Orlans, 1979). Since it is relatively easy to study the extent and kinetics of IgA transport by collecting bile, and since there is evidence that IgA and SC from different species will interact in vitro (Mach, 1970; Socken & Underdown, 1978) we have used this method to study the transport of heterologous IgA in four mammalian species. [ABSTRACT FROM AUTHOR]

A report is given of the use of the enzyme-linked immunosorbent assay to measure antibody to preparations of human thymocyte membranes (HTMA) and to β2-microglobulin. The assay described is simple and rapid, and requires only small quantities of an easily stored membrane preparation. The advantages of this technique over conventional methods involving cytotoxicity are discussed. Raised levels of 1gM antibody to β2-microglobulin were detected in sera from active lepromatous leprosy cases but not in sera from SLE patients. Raised levels of IgG and 1gM antibody to HTMA were found in sera from most active lepromatous cases. Two of eight sera from SLE patients showed raised IgG anti-HTMA, but not raised 1gM. An attempt was made to study the sub-class of the IgG antibodies found, but when checked against purified human IgG myeloma proteins, the available anti-subclass sera were found to lack the necessary degree of specificity in this assay. [ABSTRACT FROM AUTHOR]

Passively transferred MOPC 315 IgA myeloma protein accelerated the elimination of DNP-ovalbumin, to which the myeloma protein bound with antibody-like affinity, from the circulation and increased the subsequent antibody response to hapten and to carrier, when injected with or without adjuvant. [ABSTRACT FROM AUTHOR]

Polymeric myeloma IgA, labelled with 125I, was injected intravenously into rats that were killed 5, 30 or 60 min later and the livers removed, fixed and sectioned. Autoradiographs of ultra-thin sections examined in the electron microscope showed that the IgA first became bound to the plasma membrane of the hepatocytes but after 30 rain much of it was transported across their cytoplasm and became localized around the bile canaliculi. At this time, autoradiographs of 1 μm sections examined in the light microscope showed the contents of the bile ducts in the portal tracts to be labelled heavily. These results confirm the previous finding of rapid transport of IgA across the liver and show directly that the hepatocytes are the ceils that carry it out. No intracellular organelle or vesicular structure, discernible within the resolving power of the techniques used, could be implicated in the transport mechanism. [ABSTRACT FROM AUTHOR]

An antiserum raised in rabbit against MOPC 104E myeloma cells was extensively absorbed by murine IgM, thymocytes and spleen cells. Using indirect immunofluorescence, the distribution of the corresponding mouse plasma cell antigen(s)(MPCA) was determined among immunized spleen cells. Only 1–3% of the cells were stained but this MPCA-bearing subpopulation included all IgM plasma cells, a sizable proportion of IgG plasma cells and about one third of the antigen binding cells identified following deliberate immunization. It is therefore proposed that MPCA is transiently expressed during the antigen-induced differentiation of virgin B lymphocytes into memory cells as it does during the maturation process into Ig-producing cells and thus reflects the ontogenic relationship of these two differentiation pathways. Hsu & Boyse, 1971; Watanabe, Yagi & Pressman, 1971), has been used to define a mouse specific plasma cell antigen. In the absence, however, of a carefully controlled absorption of this antiserum on the bulk of B lymphocytes, the antibodies directed against the mouse B lymphocyte antigen(s), MBLA (Raff, Nase & Mitchison, 1971) are likely to contribute to its various effects on several immune functions reported so far. [ABSTRACT FROM AUTHOR]

Experiments were performed to ascertain whether IgE in different allergic sera had the same or different sensitizing properties for chopped human lung. When allergic sera were allowed to compete with myeloma IgE for tissue receptors in chopped lung and subsequently challenged with antigen, two groups of sera could be distinguished, one which competed well with myeloma IgE and one which competed poorly. Sera that competed well with myeloma IgE were also able to sensitize for greater histamine release relative to IgE concentration when sensitized lung tissue was challenged with antiIgE. The converse was true of those sera that competed poorly with myeloma IgE in the antigen assay, in that they sensitized for histamine release only at relatively high IgE concentrations in the anti-IgE assay. The possible significance of these findings is discussed. [ABSTRACT FROM AUTHOR]

Supernatants of human peripheral mononuclear cells containing membrane components shed in consequence of 4–37° temperature shift were used as source for isolation of Fc-receptors (FcR). Aggregated IgG1 mycloma protein and TMV-anti-TMV complexes proved suitable sorbents to adsorb quantitatively and specifically the FcR-s. The isolated FcR interacts only with IgG and not with IgM. No haemagglutination was observed when the isolated FcR was incubated with sensitized human Rh + red blood cells. Complement dependent lysis of sheep red blood cells was not inhibited by the isolated FcR-s. The interaction between IgG and SpA from Staphylococcus aureus (Cowan I) bacteria was not inhibited when red blood cells sensitized with IgG were preincubated with the isolated FcR-s. The differences between the FcR-like material isolated from supernatants of peripheral human mononuclear cells and those secreted by stimulated T cells or produced by lymphoblastoid cell lines are discussed. [ABSTRACT FROM AUTHOR]

The role of mouse homocytotropic antibodies in passive cutaneous anaphylaxis reaction was investigated. One class of antibody was heat stable, detected at 2 h but not at 48 h after passive transfer, and belonged to a subclass of mouse IgG. The other was heat labile, detected at 2 h and 48 h after passive transfer, and belonged to the IgE class of mouse immunoglobulins. In the presence of IgG, IgE homocytotropic antibody was not detected early after passive transfer. This was thought to be due to a masking of IgE by IgG antibodies rather than a competition for mast cell surface receptors, since inhibition studies with rat IgE myeloma protein suggested that mouse IgE and IgG1 may have different receptor sites on mast cell surfaces. [ABSTRACT FROM AUTHOR]

Possibility of inhibition of an efficient in vitro IgE-sensitization system was studied. The sensitization of mouse peritoneal mast cells with an anti-ovalbumin IgE-rich fraction of serum, as tested by ovalbumin-induced degranulation, was inhibited by previous incubation with antisera of another or of no specificity. Fractionation and other experiments showed that the inhibiting activity correlated with IgE content, IgG 1 did not seem to have an effect. Sensitization was also inhibited by rat myeloma IgE, 50 ng giving a 50 per cent inhibition. Plots of the logarithms of rat and mouse IgE concentration vs their inhibitory effect on sensitization gave two parallel linear curves, indicating that mouse and rat IgE compete for the same receptor sites. It was thus possible to use this system as a sensitive bioassay for both mouse and rat IgE levels and, by comparing inhibition by mouse IgE to that by a known rat IgE standard, to obtain not only relative data but absolute mouse IgB levels. This, and also a better discrimination of IgB doses, was the major advantage of this bioassay in relation to the equally sensitive anti-IgE degranulation tests. [ABSTRACT FROM AUTHOR]

Antisera have been raised to the Fv fragment derived from a mouse α/λ myeloma. These had different reactivities for Fv and mouse immunoglobulin and two of them appeared to detect v region framework determinants on normal mouse immunoglobulins. A large proportion of mouse lymphocytes were shown to have Fv determinants on the surface which was part of the B-lymphocyte antigen receptor. Most of the reacting cells were B lymphocytes. Fv determinants were not detected on the majority of T lymphocytes including cells with known T-helper cell activity. It is concluded that in mice, T cells do not express immunoglobulin v region framework determinants on their surface. [ABSTRACT FROM AUTHOR]

Human IgG1 Fc fragment was digested at neutral pH by thermolysin, producing two large subfragments: one comprising the major part of the Fc fragment but devoid of the hinge region; the other comprising the Cγ3 domain. The former fragment retained the capacity to react with 'general' rheumatoid factors whereas the latter did not, indicating that the binding site for 'general' rheumatoid factors on the Fc fragment of human IgG1 does not involve the hinge region of the molecule. [ABSTRACT FROM AUTHOR]

Digestion of human IgG by a new lysine-specific protease, isolated from the basidiomycete Armillaria mellea, produced Fc and Fab fragments similar to those produced by papain digestion of the same molecule. Digestion appeared to be restricted to a single cleavage point within the hinge region of the IgG molecule. Myeloma proteins of IgG1, IgG3 and IgG4 subclasses were found to be digested at an extremely rapid rate whereas IgG2 myeloma proteins appeared to be resistant to digestion by this enzyme. [ABSTRACT FROM AUTHOR]

The binding of mouse myeloma IgGl, IgG2a, IgG2b, IgGl Fc, IgG2b Fc and a pepsin produced C-terminal subfragment of IgGl Fc and IgG2b Fc (provisionally identified as pFc') to mouse peritoneal macrophages was investigated. The high affinity cytophilic antibodies belonged to IgG2 subclasses and the binding site of these antibodies was located in the GH3 homology region. [ABSTRACT FROM AUTHOR]

The patient's (Im) serum contained two myeloma proteins possessing the same heavy chains (γ1) and different light chains (κ or λ). The presence of identical antigenic determinants in the variable region of the heavy chains of both proteins raises the problem of their cellular origin. The immunofluorescence technique on bone marrow smears was used to identify the cells producing these proteins. Rabbit antisera monospecific to human κ and λ types of light chains, labelled with fluorescein or rhodamine, were applied onto the smears. These studies always revealed the presence of both κ and λ chains in the same plasma cells, thus suggesting that single cells of this patient are capable of synthesizing both IgGl (κ) and IgGl(λ) proteins. [ABSTRACT FROM AUTHOR]

We have determined the circular dichroism of sixteen human IgG myeloma proteins, representative of the four subclasses. No significant variation in β structure was observed between the subclasses. However, at wavelengths greater than 230 nm, the spectra of IgG3 myeloma proteins is quite distinct, indicating a unique conformation. Myeloma proteins of the other subclasses gave similar overall spectra, but some of the features of the negative maxima in the region of 260-280 nm appeared to be subclass-specific. [ABSTRACT FROM AUTHOR]

Three human polymeric IgA (pIgA) myeloma proteins of tetrameric size were compared for their J-chain content, their in vitro secretory component (SC)-binding ability, and their capacity to be transcytosed by polymeric immunoglobulin receptor (pIgR)-expressing epithelial cells in vitro and rat hepatocytes in vivo. One of the three pIgA preparations, pIgA-L, was shown to lack J chain and was unable to combine with purified free human and rat SC, whereas pIgA-G and pIgA-C contained J chain and combined readily with SC. Furthermore, pIgA-L was not transferred into rat bile after intravenous injection, and was hardly transported apically by polarized Madin–Darbey canine kidney cell monolayers expressing the human pIgR, whereas pIgA-G and pIgA-C were efficiently transported in both test systems. Together with our recent demonstration that antibodies to human J chain block the SC/pIgR-mediated epithelial transport of pIgA, these data unanimously confirm the proposed key role of J chain in the epithelial transport of polymeric immunoglobulins into exocrine secretions. [ABSTRACT FROM AUTHOR]

Circulating IgG autoantibodies to myeloperoxidase (MPO) are associated with renal vasculitis and have been implicated in its pathogenesis. However, raised levels of these autoantibodies may persist during clinical remission. We tested whether this paradox could be explained by immunoglobulin subclass switching during disease evolution, since different subclasses have different immunological and biochemical properties. Sera with anti-myeloperoxidase (anti-MPO) activity from 33 patients with active disease and 20 anti-MPO positive follow-up sera were studied by an ELISA using a panel of anti-human IgG subclass monoclonal reagents previously calibrated on human myeloma proteins. Anti-MPO subclass distribution in initial sera was: IgG1, 31 (94%); IgG2, 10 (30%); IgG3, 24 (73%); and IgG4, 22 (67%). IgG3 anti-MPO decreased during follow-up (P <0.02), with no change in IgG1 and IgG4. Relative functional affinity of anti-MPO antibodies in purified IgG subclasses was studied by the diethylamine method. IgG3 fractions consistently had a greater affinity for MPO than the other subclasses. Sequential studies in four patients demonstrated an affinity maturation for IgG1 and IgG4 anti-MPO as IgG3 anti-MPO disappeared. We conclude that dynamic changes of subclass distribution and affinity may explain discrepancies between anti-MPO antibody titre and disease expression. [ABSTRACT FROM AUTHOR]

To assess the specificity of anti-nuclear antibodies with cross-reactive rheumatoid factor (RF) activity, monoclonal anti-DNA and anti-Sm antibodies from MRL-lpr/lpr mice were tested for binding to a variety of IgG antigens. These antibodies had all been previously identified as binding heterologous IgG. By ELISA, antibodies in this panel all bound BALB/c myeloma proteins representing the different IgG subclasses, indicating broad reactivity with murine IgG as well as heterologous IgG. The determinant recognized by these antibodies was further investigated using the Fab, F(ab')2 and Fc fragments of both human as well as rabbit origin. All antibodies bound well to fragments as well as intact IgG antigens. These antibodies were further analysed by Western blotting, demonstrating that most bound to both heavy and light chains of human origin. Together, these observations suggest that some anti-nuclear antibodies bind a conserved antigenic determinant present widely on immunoglobulin chains. This determinant may represent a common sequence important in immunoglobulin domain structure. [ABSTRACT FROM AUTHOR]

We raised anti-VH315 antibodies by immunization of rabbits with VH315 fragments, the variable portions of the immunoglobulin heavy chains of MOPC315 myeloma protein. Inhibition radioimmu-noassay using various immunoglobulins as inhibitors showed that the anti-VH315 antibodies specifically reacted with the variable portions of the heavy chains of MOPC315 myeloma protein. When the variable region (VH) gene of the heavy chains was cloned and sequenced from the cells producing the heavy chains detected by the anti-VH315 antibodies, the VH gene was closely related (82% homology at amino acid level) to the VH gene of MOPC315, When we examined the frequency with which the variable region(s) detected by the anti-VH315 antibodies were expressed in eight Ig- null Abelson virus-transformed cell lines (DJ/DJ or VDJ-/DJ). which were able to generate functional V regions during culture, only one cell line, ATB-1, produced a small number of intracytoplasmic/μ-positive cells (VH315+ cells) stained by the anti-VH315 antibodies. The percentage of the total number of the VH315+ cells to the total number of intracytoplasmic μ-positive cells was 0·91% in AT8-1. In the remaining seven cell lines, no VH315+ cells were detected. In the present study we estimate, for the first time at the individual cell level, the frequency of the utilization of the heavy chain variable region(s) identical or closely related to that of MOPC315 in the functional V region formation during early B-cell development. [ABSTRACT FROM AUTHOR]

We have previously shown that that idiotype (Id) repertoire expressed by old mice is different from that of young mice after immunization with trinitrophenylated Ficoll. Older mice also produce more auto-anti-Id antibodies than do young mice. Mice surviving a normally lethal dose of radiation (800 rads) as result of partial shielding of their bone marrow slowly recover immune function, after the repopulation of their peripheral lymphoid system by bone marrow precursor cells. Aged mice subjected to such a procedure produce low auto-anti-ld responses, like those of young mice. However, transfer of splenic T cells from old donors into such mice increases the magnitude of the auto-anti-Id response. In the present studies, we show that the age-related shift in Id expression is also determined by the age of the donor T veils. Furthermore, we show in serial cell transfer studies that the peripheral T-cell population of old mice modifies the level of the auto-anti-ld response in the absence of antigen. The results thus provide evidence for the normal, in vivo, operation of an Id-anti-Id network between B and T lymphocytes. [ABSTRACT FROM AUTHOR]

We have previously reported that the immunization of BALB/c mice with MOPC-104E myeloma protein (M104E) induced idiotype-sjjecific Ly 1-negative B lymphocytes that had an ability to enhance idiotype-,positive anti-dextran antibody production. It was also shown that the cell interaction between idiotypic and anti-idiotypic B lymphocytes was observed in a class Il-restricted manner. The effect of monoclonal anti-class II antibody on the B-B cell interaction is investigated in this report. The addition of anti-I-A or anti-I-E monoclonal antibody into the B-B cell interaction system, from both BALB/c (H-2d) and BALB.K (H-2k), inhibited the enhanced antibody production mediated by idiotype-immune B lymphocytes. Interestingly, however, it was revealed that the anti-IA and anti-I-E antibodies acted differently on each B-lymphocyte population. Pretreatment of an anti-idiotypic (idiotype-immune) enhancing B-lymphocyte population with anti-I-A antibody diminished its enhancing activity, while anti-I-E did not. On the other hand, pretreatment of dextranimmune antibody producing B cells with anti-I-A antibody showed no effect, while anti-I-E inhibited anti-dextran antibody production. When the enhancing B-lymphocyte population of F1 mice was treated with anti-I-A antibody specific for one of their parents' haplotypes, co-operation with the respective haplotype B cells was inhibited, but the other haplotype was not. The inhibitory effect of anti-class II antibodies could only be seen at the early phase of culture period. Taken together, the results of these experiments suggest that the class II antigens are concemed with the self-recognitive cell interaction among B lymphocytes in the frame of idiotype network systems. [ABSTRACT FROM AUTHOR]

An auto-anti-IgE response was induced in conventional (PVG-RT1U and high IgE-producing (BN) rat strains by immunization with a highly purified rat IgE myeloma IR2. Earlier work established that total serum IgE levels were decreased by this procedure (Marshall & Bell, 1985) but only in the PVG-RTIU strain. IR2-immunized rats were tested for their ability to produce a specific IgE response to ovalbumin (OVA). The primary anti-OVA IgE response was inhibited by 60-75% in both rat strains, regardless of whether the total serum levels of IgE were reduced. The secondary IgE response to OVA was also inhibited in anti-IgE-producing animals but not in rats primed with OVA before anti-IgE induction. The inhibition of the anti-OVA response was isotype specific; the IgG response to OVA was unaffected. These studies may help elucidate the regulatory role played by naturally occurring anti-IgE antibodies found particularly in atopic individuals. [ABSTRACT FROM AUTHOR]

In the present study we have investigated whether bovine erythrocytes (Eb) specifically sensitized with human polyclonal IgA l (EbIgA 1) are able to bind to resident adherent rat peritoneal cells (PMø). Rat PMø formed rosettes with Eb-IgAl at room temperature and at 37°. The formation of these rosettes could be blocked completely by excess human serum IgA or myeloma IgAl. In contrast, human IgG or rat IgG did not inhibit the formation of rosettes, whereas human polymeric myeloma IgA2 only partially inhibited rosette formation. Complete inhibition of rosette formation was also induced by rat monomeric and polymeric myeloma IgA, suggesting species interchangeability. Furthermore, rosette formation could be completely blocked in the presence of excess asialofetuin or D-galactose, while excess ovalbumin or D-mannose had no effect. These results suggest that the oligosaccharides in the hinge region of human IgAl are involved in the binding of Eb-IgAI to rat PMø. [ABSTRACT FROM AUTHOR]

Normal IgG preparations of human, rabbit or guinea-pig origin (IgG2) were tested for their capacity to inhibit the cytotoxicity of purified human lymphocytes, as induced by rabbit IgG antibodies to chicken erythrocytes. All IgGs were found to be about equally efficient inhibitors. Human F(ab′)2 used for control, gave no inhibition. Human myeloma proteins of subclasses IgG1, IgG2 and IgG3, were about equally efficient inhibitors. In contrast, the inhibitory action of myeloma proteins belonging to subclass IgG4 was weak and more irregular. In this assay system, a large excess (∼ 106 × ) of normal IgG over antibodies had to be added in order to achieve ≥ 50 per cent inhibition. Heating of the inhibitors to 63° for 30 minutes did not significantly enhance their inhibitory capacity. For comparison, the same human IgG preparations and myeloma proteins were also tested for their capacity to inhibit phagocytosis by human blood monocytes of chicken erythrocytes sensitized with rabbit IgG antibody. As was to be expected in this system, only HGG, IgG1 and IgG3 caused inhibition whereas F(ab′)2, IgG2 and IgG4 were completely negative. [ABSTRACT FROM AUTHOR]

Anti-γ-globulin antibodies which show specificity for γG1 and γG3 subclass antigens respectively have been detected in human sera. In contrast to most of the subclass antigens which are present in intact γ-globulin, these antigens are only revealed by pepsin digestion. This is the first test system employing human anti-γ-globulin antibodies for determining γG subclasses of isolated antibodies and myeloma proteins. These anti-γ-globulins also react strongly with autologous pepsin-digested γG-globulin. The finding of human anti-γ-globulin antibodies with these fine specificities for γG subclasses and autologous γG-globulin suggests that their function is closely related to certain specific-γG antibody populations. The findings show that both γG3 and γG1 molecules have subclass specific antigenic structures which are revealed following pepsin digestion. [ABSTRACT FROM AUTHOR]

The catabolism of myeloma proteins: of the γG-subclasses γG1 and γG2 were measured in a healthy volunteer and contrasted with that of γG-globulin preparations containing all four subclasses and isolated from various sources. The γG2 protein had a biological half-life of 24 days, showing no evidence of catabolic heterogeneity as measured over a period of 7 weeks. In contrast, the γG1 protein showed some catabolic heterogeneity, the half-life increasing from 15 to 19 days over the same period. It is possible that molecules of γG1-globulins may exist in different conformational forms. The catabolism of whole γG-globulin is heterogeneous. This can be substantially explained in terms of the resultant catabolic pattern of mixtures of γG1- and γG2globulin molecules. [ABSTRACT FROM AUTHOR]

The IgD-immunoglobulin producing plasma cells oft human spleens have been localized with specific antisera and the type of the light chains present in each of them has been determined by sequential staining with anti-K and anti-L antisera. About 87 per cent of IgD cells have L-type light chains. This is in accord with the prevalence of L-type light chains in IgD myeloma proteins. [ABSTRACT FROM AUTHOR]

Interactions between a rheumatoid factor preparation and native human (normal and myeloma) and animal γG-globulins have been studied in the ultracentrifuge. Using pooled normal γG-globulin or a myeloma γG-globulin, the extent of reaction has been shown to be dependent upon the reactant concentration employed, a four-fold excess, by weight, of γG-globulin over rheumatoid factor being required to ensure maximum production of 22S complex. All native myeloma γG-globulins tested reacted to give a 22S complex, the majority showing similar reactivity to the normal γG-globulin control. A small proportion, however, showed significantly different reactivities. Of the animal γG-globulins tested, only rhesus monkey γG-globulin showed reactivity similar to human γG-globulin. The other species showed decreased reactivity. The importance of these findings is discussed. [ABSTRACT FROM AUTHOR]

A new class of normal immunoglobulin corresponding to a myeloma protein (myeloma-IgND), which fails to react with specific antisera to IgA, D, G and M (Johansson and Bennich, 1967) was detected in serum from sixty-two blood donors using a radio-immunosorbent technique (Wide and Porath, 1966) IgND in normal sera corresponds to myeloma-IgND on electrophoresis, gel filtration and DEAE-chromatography. Isolated IgND gave a reaction of identity with myeloma-IgND in Ouchterlony gel diffusion analysis. The concentrations of IgND in 93 5 per cent of the samples was within the range of 100–700 ng/mL. Normal levels of IgND were found in four samples apparently lacking IgA and/or IgD as determined by single radial immunodiffusion. Elevated levels of IgND were found in four samples one of which was from a subject with previously undiagnosed extrinsic asthma. It is concluded that myeloma-IgND represents a new class of human immunoglobulin.

An 8S myeloma component, isolated from serum of a patient with myelomatosis is described, which appears to have no antigenic determinants in common with human α-, δ-, γ- or μ-polypeptide chains as revealed by immuno-electrophoresis and Ouchterlony gel diffusion analysis. The myeloma protein migrates in the fast γ-region on electrophoresis at pH 8·6 and has an elution volume on Sephadex G-200 similar to that of 6·5S IgA. The isolated myeloma component has an approximate molecular weight of 200,000 and a total carbohydrate content of 10·7 per cent. Reduction with β-mercaptoethanol and acid dissociation yields light polypeptide chains of Type L and a carbohydrate-rich component, in the ratio of 1:4. Antisera specific to determinants on the heavy chains of the myeloma protein showed no reaction with the immunoglobulins A, D, G or M. Instead unique determinants were found on the heavy polypeptide chains. [ABSTRACT FROM AUTHOR]

A case of multiple myeloma with pyroglobulinaemia is reviewed. Certain physical, immunological and chemical characteristics of the pyroglobulin are described. The pyroglobulin precipitate has been shown to bind complement, react with rheumatoid factor, produce passive cutaneous anaphylaxis, generalized passive anaphylaxis and passive Arthus-type reactions. In spite of this experimental demonstration of biological activity of the precipitated pyroglobulin, no clinical abnormality appeared to result from the presence of the myeloma pyroglobulin in the patient. [ABSTRACT FROM AUTHOR]

Studies of the distribution of antibody-combining sites, anticomplementary and genetic activity in the papain digestion products of normal γ globulins and myeloma proteins have been carried out. The segregation of biological and chemical properties in the chromatographically separated fractions of the papain digests has been noted. Starch-gel electrophoretic studies indicate the complexity of the molecules of normal γ2 globulins and of myeloma proteins and indicate physico-chemical relationships between these types of molecules. Certain similarities in biological properties are also noted. [ABSTRACT FROM AUTHOR]

Although normal γ1A (β1A) globulins, myeloma proteins, as well as Bence-Jones proteins and normal human urine 7S γ globulins cross-react with 7S γ globulins, none of these proteins can sensitize the skin of the guinea-pig to give a reverse passive cutaneous anaphylaxis reaction. The 3.5S fragments of human antisera to horse serum proteins can no longer give passive cutaneous anaphylaxis reactions, but fragment C and probably A can inhibit the passive cutaneous anaphylaxis reaction of die original antiserum. By reverse passive cutaneous anaphylaxis, negative results were obtained with each of the three fragments or the 5S pepsin digest. [ABSTRACT FROM AUTHOR]

We have investigated the ability of an antisense oligonucleotide (ASE- 1) to specifically inhibit IgE synthesis by a human myeloma cell line, U266. ASE- 1 inhibited IgE production in a concentration- dependent manner, as assessed by isotype-specific ELISA measurement of immunoglobulin in myeloma cell supernatants. Inhibition of IgE production was specific and not due to cytotoxicity since IgG1 and IgM production by human myeloma cell lines ARH-77 and RPMI-1788 respectively, was not significantly affected by up to 20 μM ASE-1 whereas IgE production was inhibited by approximately 70% at this concentration. These results indicate that antisense oligonucleotides represent a potential therapeutic approach to the treatment of IgE-mediated allergic diseases. [ABSTRACT FROM AUTHOR]

Focuses on the four major groups of human immunoglobulin molecules as suggested by a Committee on Nomenclature for Human Immunoglobulins. Subclasses of the major groups; Notation for the immunoglobulin G subclasses; Designation on the heavy chain of the Vi myeloma protein.