Idiotype regulation of thymus autoantibodies

Rabbit antisera specific for idiotypic determinants (Id) of monoclonal Thy-1 autoantibodies were tested for their capacity to elicit Id-bearing thymus autoantibodies in mice. Rabbits were immunized with the 20-10-5 monoclonal IgM Thy-1 autoantibody, and idiotype-specific antibodies (anti-Id) were obtained by affinity chromatography. BALB/c and C3H mice were immunized by repeated i.p. injections of the anti-Id reagent. Control mice received repeated injections of purified normal rabbit immunoglobulin (NRIg) sheep red blood cells (SRBC) or human serum albumin (HSA). The sera of the treated mice were examined for their reactivity with anti-Id xenoantisera and for their capacity to react with thymus cells. The injection of anti-Id sera into either BALB/c or C3H mice resulted in a significant increase in the serum concentration of Id-bearing immunoglobulins, while no such change was observed in the sera of mice injected with NRIg. The administration of anti-Id, NRIg, SRBC or HSA resulted in a gradual increase in the concentration of autoantibodies reactive with thymus cells. Incubation with anti-Id sera prevented the binding to thymus cells of autoantibodies induced by anti-Id treatment. In contrast, the binding capacity of autoantibodies induced by NRIg, SRBC or HSA was unaffected by anti-Id sera. Thus, only the thymus autoantibodies induced by anti-Id treatment expressed Id-determinants. These results demonstrate the existence of a regulatory network in the formation of thymus autoantibodies.