Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells
- Author(s)
- Enders, A; Bouillet, P; Puthalakath, H; Xu, YK; Tarlinton, DM; Strasser, A;
- Details
- Publication Year 2003-10-06,Volume 198,Issue #7,Page 1119-1126
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Publication Type
- Journal Article
- Abstract
- During 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.
- Publisher
- ROCKEFELLER UNIV PRESS
- Keywords
- PERIPHERAL DELETION; NEGATIVE SELECTION; T-CELLS; ANTIGEN; ELIMINATION; LYMPHOCYTES; DEATH; EXPRESSION; TOLERANCE; MICE
- Publisher's Version
- https://doi.org/10.1084/jem.20030411
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2003-10-06 12:00:00