Enders, AnselmBouillet, PhilippePuthalakath, HamsaXu, YeukangTarlinton, David M.Strasser, Andreas2015-12-070022-1007http://hdl.handle.net/1885/22972During development, the stochastic process assembling the genes encoding antigen receptors invariably generates B and T lymphocytes that can recognize self-antigens. Several mechanisms have evolved to prevent the activation of these cells and the concomitant development of autoimmune disease. One such mechanism is the induction of apoptosis in developing or mature B cells by engagement of the B cell antigen receptor (BCR) in the absence of T cell help. Here we report that B lymphocytes lacking the pro-apoptotic Bcl-2 family member Bim are refractory to apoptosis induced by BCR ligation in vitro. The loss of Bim also inhibited deletion of autoreactive B cells in vivo in two transgenic systems of B cell tolerance, Bim loss prevented deletion of autoreactive B cells induced by soluble self-antigen and promoted accumulation of self-reactive B cells developing in the presence of membrane-bound self-antigen, although their numbers were considerably lower compared with antigen-free mice. Mechanistically, we determined that BCR ligation promoted interaction of Bim with Bcl-2, inhibiting its survival function. These findings demonstrate that Bim is a critical player in BCR-mediated apoptosis and in B lymphocyte deletion.Keywords: autoantigen; B lymphocyte antigen; b lymphocyte antigen receptor; B lymphocyte receptor; BIM protein; cell protein; protein bcl 2; unclassified drug; animal cell; antigen recognition; apoptosis; article; autoimmunity; B lymphocyte; B lymphocyte deletion; Apoptosis; Autoimmunity; Gene knockout; Tolerance; Transgenic mice200310.1084/jem.200304112015-12-07