Similar Idiotypic Specificities in Immunoglobulin Fractions with Different Antibody Functions or Even without Detectable Antibody Function

Oudin, J; Cazenave, Pierre‐André

doi:10.1073/pnas.68.10.2616

Cited by 201 publications

(67 citation statements)

References 20 publications

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“…The H130 idiotypic family seems, therefore, to encompass a group of antibodies, the majority of which do not bind to DNA. There are other examples of idiotypes that are shared by antibodies with different antigen-binding specificities (18)(19)(20)(21). This observation conforms with Jerne's (22) network hypothesis, which postulates regulation of the immune response by anti-idiotypic antibody (Ab2) reacting with idiotypes (Abl) that are induced by antigenic stimulation.…”

Section: Discussionsupporting

confidence: 69%

“…3B) (Table 4). The major portion of the three idiotypes, however, did not bind DNA; 18-day gestation) were carefully prepared to avoid contamination by maternal blood cells (9), cultured for 5 days in the presence or absence of LPS, and then labeled for 4 hrwith ['5Slmethionine. Values represent results of two experiments, expressed as net cpm (mean + SEM) in immunoprecipitates of 0.5 ml of culture supernatant (107 cells were labeled in 1 ml).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Normal mice express idiotypes related to autoantibody idiotypes of lupus mice

Datta

Stollar

Schwartz

1983

Proc. Natl. Acad. Sci. U.S.A.

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Spleen and fetal liver B cells of normal mice synthesized idiotypes shared by anti-DNA autoantibodies of genetically autoimmune mice. Some of the idiotypes were specific for DNA; the majority, however, were not. The findings indicate that the autoantibody idiotypes are related to a conserved family of antibody variable regions that are present in normal animals.The spontaneous production of autoantibodies to DNA is characteristic of human and murine systemic lupus erythematosus (1,2). These antibodies have been implicated in the pathogenesis of nephritis and other lesions of the disease (1, 2). Their production, however, is not restricted to mice that develop systemic lupus erythematosus. Strains of normal mice can spontaneously produce such antibodies in old age (3) or upon stimulation of their B cells by the polyclonal activator lipopolysaccharide (LPS) (4, 5). These observations have an important bearing on the origins of anti-DNA autoantibodies. Do the autoantibodies produced by autoimmune strains differ from their counterparts in normal strains? Are the same anti-DNA antibody-producing clones of cells present in both autoinmmune and normal strains? We addressed these questions by determining if normal mice can produce antibodies with idiotypic markers ofthe anti-DNA autoantibodies ofMRL-lpr/lpr (MRL/lpr) mice, a strain that develops a lethal form of systemic lupus erythematosus (1). Three idiotypic markers, designated H130, H102, and H43, were studied. These autoantibody variable (V) region markers were previously identified by rabbit anti-idiotypic sera that are specific for the antigen combining sites of the corresponding MRL/lpr-derived monoclonal anti-DNA antibodies (6). All MRL/lpr mice produce large amounts of H130, which is a prominent idiotype of the anti-DNA autoantibodies of that strain. H102 and H43 are produced in smaller amounts and their serum concentrations do not rise during the course of the autoimmune disease (7). MATERIALS AND METHODSAnimals and Antibodies. All mice came from The Jackson Laboratory. Establishment of the monoclonal anti-DNA antibody-producing hybridomas H130, H102, and H43 from fusions of MRL/lpr spleen cells, purification of the antibodies, and production of the rabbit antisera specific for their idiotypes were previously described (6)(7)(8). The anti-idiotypic antibodies were prepared by absorption of the rabbit antisera successively on the following affinity columns: purified mouse IgM-IgGSepharose, Sepharose-bound globulins of MPC-11 ascites fluids, and Sepharose-bound globulins of pristane-induced (AKR x DBA/2)F1 ascites fluid. The pooled flow-through fractions were repeatedly absorbed on the columns until the acid eluates (0.5 M acetic acid) from each column had an Am.s less than 0.001.The absorbed anti-idiotypic reagents were further purified on a goat anti-rabbit IgG-Sepharose column with acetic acid as the eluting agent. The three anti-idiotypic antibodies were found to be specific for the respective monoclonal anti-DNA antibody idiotypes (H130, H102, and...

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Section: Discussionsupporting

confidence: 69%

Section: Methodsmentioning

confidence: 99%

Normal mice express idiotypes related to autoantibody idiotypes of lupus mice

Datta

Stollar

Schwartz

1983

Proc. Natl. Acad. Sci. U.S.A.

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“…We selected alloantisera from four hyperimmunized renal dialysis patients BY-10 and, to a lesser extent, BY-2 blocked the binding to histone and dsDNA; BY-10, unlike BY-2, recognized antihistone Ids expressed by the IgG isolated from sample QCA84 (active-phase SLE), but do not seem to recognize the antidsDNA Ids expressed by the same fraction. The expression of cross-reactive Ids (CRIs) has been shown for antibodies with different specificity [16] and among natural and disease-specific autoantibodies [17]. Another possibility, which we consider to be more likely, is that polyreactive antibodies recognize different Ids in the same way that they bind to different antigens; this phenomenon has been called multireactivity anti-Id [18].…”

Section: Effect Of Human Monoclonal Igm On the Binding Of Anti-hla Iggmentioning

confidence: 98%

Human Polyreactive IgM Monoclonal Antibodies with Blocking Activity Against Self‐Reactive IgG

et al. 1997

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Natural IgM antibodies have been found to be involved in the control of IgG reactivity in normal serum. The authors investigated the blocking activity of four human IgM monoclonal antibodies (BY-2, BY-7, BY-10 and IRM-7) derived from B-cells from blood samples of three renal dialysis patients, which had shown multispecific properties similar to those observed for natural polyreactive autoantibodies. To achieve this, competitive inhibition assays were performed with these MoAbs on the binding of IgG purified from a healthy control, three patients with SLE, and two patients with autoimmune thyroiditis, to histone, dsDNA, RNP and thyroglobulin. MoAbs inhibited binding of self-reactive IgG to histone and dsDNA, but not to thyroglobulin or RNP, of natural and active or inactive phase disease-associated autoreactive IgG. The inhibitory effect of the MoAbs was mediated by V-region dependent interactions with autoreactive IgG, as shown by the ability of these MoAbs to block the binding of F(ab 0 ) 2 fragments of autoreactive IgG to antigens (histone and dsDNA). The blocking of autoantibody activity was dose-dependent with maximal inhibition occurring at a specific molar ratio between the patient's IgG and a given MoAb. In contrast, MoAbs did not inhibit binding of IgG alloantibodies present in the sera of four polytransfused renal dialysis patients to target antigens on the surface of different cells. These results support the concept of a functional idiotypic network regulating autoimmune responses, and suggest that the IgM MoAbs under study may be natural polyreactive antibodies belonging to the physiological network of autoantibodies with highly connected V-regions, capable of binding and functionally neutralizing V-regions of natural and pathologic autoantibodies.

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“…First, one can argue that sharing of idiotypic determinants indicates similarity, but not necessarily identity of variable region structure. Numerous examples exist of immunoglobulins with different specificities or different variable region sequences sharing idiotypic determinants (43,44). In fact, recent work from this laboratory demonstrates that differences do exist between idiotypes on anti-PC antibodies of different IgG subclasses.…”

Section: Isotype Distribution Of Antibodies To Ti-1 Ti-2 and Thumusmentioning

confidence: 99%

Subclass restriction of murine antibodies. II. The IgG plaque-forming cell response to thymus-independent type 1 and type 2 antigens in normal mice and mice expressing an X-linked immunodeficiency.

Slack¹,

Der-Balian²,

Nahm³

et al. 1980

The Journal of Experimental Medicine

246

134

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Antigens have been classified previously into three categories, thymus-dependent (TD), thymus-independent type (TI) 1, and TI-2, based upon thymic dependence and ability to stimulate an immunodeficient strain of mouse, CBA/N. Here we demonstrate that the different antigen classes elicit IgG antibodies of different subclasses. TD antigens stimulate predominantly IgG1 antibodies, with smaller amounts of IgG2 and IgG3 being expressed. TI-1 antigens stimulate almost no IgG1 antibodies and equal amounts of IgG2 and IgG3. TI-2 antigens elicit predominantly IgG3 antibodies. Mice expressing the CBA/N phenotype are known to be nonresponsive to TI-2 antigens. This was confirmed in this study. In addition, we demonstrate that the IgG3 component of the response to TI-1 antigens is virtually absent in mice expressing the CBA/N phenotype, which supports our previous finding that the CBA/N defect may be restricted to a B-lymphocyte subpopulation containing most of the precursors of IgG3-secreting cells.

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Similar Idiotypic Specificities in Immunoglobulin Fractions with Different Antibody Functions or Even without Detectable Antibody Function

Cited by 201 publications

References 20 publications

Normal mice express idiotypes related to autoantibody idiotypes of lupus mice

Normal mice express idiotypes related to autoantibody idiotypes of lupus mice

Human Polyreactive IgM Monoclonal Antibodies with Blocking Activity Against Self‐Reactive IgG

Subclass restriction of murine antibodies. II. The IgG plaque-forming cell response to thymus-independent type 1 and type 2 antigens in normal mice and mice expressing an X-linked immunodeficiency.

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