Parallel sets of autoantibodies in MRL-lpr/lpr mice. An anti-DNA, anti-SmRNP, anti-gp70 network

Abstract

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.