Recent advances in the understanding of the collaboration between T cells and B cells have provided a novel framework within which to analyse the mechanisms of B-cell tolerance and its breakdown. Of particular interest has been the finding that B cell anergy is due to defective antigen receptor mediated functions, while the antigen-processing machinery and CD40-dependent activation pathways are unaffected. Thus, the anergic B cell, which otherwise has a short lifespan, can be rescued by a number of regimes to participate in autoimmune responses.