Induction of autoantibodies to thyroglobulin by anti-idiotypic antibodies

We report on the induction of autoantibodies to thyroglobulin (Tg) and idiotype-positive molecules (Id') in naive BALB/c mice and Buffalo (BUF) rats after immunization with affinity-purified rabbit anti-Id antibodies directed against the Id of a mouse monoclonal antibody ( mAb62 ) specific for a hormone-containing epitope of Tg. Autoantibodies to Tg were produced in about one-half of anti-Id immunized mice, whereas Id' was detected in all but one mouse. Autoantibodies to Tg and Id' were not produced in control mice similarly immunized with non-anti-Id Ig. To clarify the relationship between molecules with Tg-binding activity and those referred to as Id', Tg-specific monoclonal antibodies were generated from an anti-Id-immunized mouse. By competitive inhibition experiments, we could determine that they were idiotypically very similar to the monoclonal antibody ( mAb62 ) at the origin of the immunologic cascade. Thus, autoantibodies induced by anti-idiotypic immunization alone are likely to be of the Ab1' type. Similarly, autoantibody to Tg and Id' molecules were induced in young normal rats of the autoimmune-prone BUF strain. Together, these results suggest that antibodies to Id directed against autoantigens are sufficient per se to activate self-reactivity.