Generation and Regulation of B Cell Autoreactivity Arising in the Periphery

Recent work on the role of environmental antigens in activating autoreactivity underscores a potentially confounding complication to current models of peripheral tolerance. Cross-reactive B cells that bind both autoantigen and foreign antigen are capable of mediating tissue damage, yet may be subject to positive selection as a consequence of interaction with antigen and T cell help. This discussion will review our work with cross-reactive antibodies and suggest a hypothesis to explain their generation and subsequent regulation.