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T cell-independent rescue of B lymphocytes from peripheral immune tolerance

Kouskoff, V., Lacaud, G., and Nemazee, D.

Science 287:2501.

In this study the authors address the question of what triggers are required to break self tolerance and generate autoantibodies. The authors engineered mice to express B cells specific for a self antigen expressed in the liver. Normally these B cells are eliminated from the periphery when they encounter the self antigen. However when these mice are immunized with a bacteriophage that expresses a peptide mimic of the self antigen, self-tolerance is broken and the mice now make autoantibody. The production of the autoantibody was independent of T-cell help as it could be elicited in mice lacking T-cells. These experiments add support to the concept that microbial infection can cause a breakdown in self-tolerance and might initiate autoimmune disease.