VIRUS-INDUCED AUTOANTIBODY RESPONSE TO A TRANSGENIC VIRAL-ANTIGEN

THE induction of autoantibodies and their possible role in the pathogenesis of autoimmune disease are poorly understood. Involvement of infectious agents has been suspected, but direct evidence is sparse1-4. Whether immunological unresponsiveness to self by antibody-forming ? cells is maintained by clonal abortion5, clonal anergy6-8 or suppression9, or how the scenario of interactions between helper T cells, B cells and antigen-presenting cells10,11-13 is distorted in autoantibody responses, is being analysed and widely debated3,6-8,14-17. To evaluate tolerance of neutralizing B-cell responses12,18 we used transgenic mice expressing the cell membrane associated glycoprotein (G) of vesicular stomatitis virus (VSV) as self-antigen. We show that autoantibodies to VSV-G cannot be induced by VSV-G in adjuvant or by recombinant vaccinia virus expressing VSV-G, but are triggered by infection with wild-type VSV. The data show that helper T-cell tolerance is crucial in maintenance of B-cell non-reactivity2,16,19,20 and that cognate T-B recognition is necessary to break tolerance of self-reactive B cells. These results may help to understand mechanisms of virus-induced autoimmunity. © 1990 Nature Publishing Group.