THE REGULATION OF SELF-REACTIVE B-CELLS

Self-reactive B cells are eliminated in a series of checkpoints that a re triggered by antigen binding. Recent reports have shown that in add ition to the processes of elimination at the immature B-cell stage, B- cell anergy and regulation of T-cell help, self-reactive cells are als o controlled by follicular competition, Fas-mediated elimination by T cells and censoring in the germinal centres. Each checkpoint operates at a threshold that reflects the need to maintain immune diversity at the same time as suppressing autoimmune disease. Analysis of the mothe aten mutation has given a direct demonstration of how such thresholds can be modulated by genetic effects.