Parallel sets of autoantibodies in MRL-lpr/lpr mice. An anti-DNA, anti-SmRNP, anti-gp70 network.
The public idiotype Id-H130 occurs in MRL-lpr/lpr serum both on a high proportion of anti-DNA autoantibodies as well as on antibodies that do not bind to DNA. To define members of the latter population, we prepared hybridomas and selected Id-H130+ mAbs that did not bind to DNA. One such antibody, mAb 28/12, was found to be an anti-SmRNP antibody. To determine whether mAb 28/12 had rheumatoid factor activity, we tested its ability to bind, in a solid-phase assay, to 16 mouse IgM mAbs. mAb 28/12 bound to only four of the panel, two anti-DNA antibodies (mAbs 512 and 319) and two anti-gp70 antibodies (mAbs 514 and 1417). In a liquid-phase competition assay with a panel of 32 monoclonal IgM and IgG antibodies, including allotype-matched Igs, mAb 28/12 reacted only with mAbs 512, 319, 514, and 1417. The binding of mAb 28/12 to mAbs 512 and 319 was displaced by DNA, but not by RNA, indicating that the idiotype it defines (Id-28/12) is in the antigen-binding region of the two anti-DNA antibodies. In the two anti-gp70 antibodies (mAbs 514 and 1417), Id-28/12 seems to occur in the framework region. To determine if all four Id-28/12+ antibodies shared a common antigen-binding property, they were tested for their ability to react with DNA and gp70. The two anti-gp70 antibodies did not bind to DNA. However, the two anti-DNA antibodies were found to immunoprecipitate viral proteins from retrovirus-infected cells. mAb 512 reacted with gp70, both in cell membrane lysates and in purified form; mAb 319 reacted with gp85, which contains both gp70 and the retroviral protein p15. Antibodies with properties similar to those of mAb 28/12 were found in MRL-lpr/lpr serum. It was possible, by affinity chromatography on an anti-gp70 antibody column, to isolate from serum those anti-(anti-gp70) antibodies with anti-SmRNP activity. These results show that parallel sets of autoantibodies, which share a common idiotype, but which bind to different autoantigens, occur in MRL-lpr/lpr mice. Some populations of anti-DNA, anti-SmRNP, and anti-gp70 antibodies appear to constitute a network of autoantibodies in that strain. We speculate that part of the anti-SmRNP population of autoantibodies can arise by mutation of germline-encoded anti-DNA antibodies.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D004247:DNA / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D012190:Retroviridae / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear; D014764:Viral Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000941:Antigens; D000956:Antigens, Viral; D001323:Autoantibodies; D001324:Autoantigens; D006023:Glycoproteins; D007130:Immunoglobulin Idiotypes; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D014764:Viral Proteins; C033589:glycoprotein gp70, murine serum; D004247:DNA