[Mechanisms for B cell tolerance and their defects in systemic autoimmune diseases]

Lines of evidence suggest that self-reactive B cells are deleted or functionally inactivated at the several different steps of maturation from immature B cells to antibody producing cells. These self-tolerance mechanisms appear to involve B cell apoptosis induced by signaling via the antigen receptor (surface immunoglobulin) or Fas. In mice prone to systemic autoimmune diseases such as bcl-2 transgenic, NZB or (NZB x NZW) F1 mice, antigen receptor-mediated B cell apoptosis is defective. In another autoimmunity-prone mice MRL/lpr, autoantibody production requires defects of Fas in B cells. These findings strongly suggest that the defects in B cell tolerance play an important role in the pathogenesis of systemic autoimmune diseases.