Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells
- Author(s)
- Fischer, SF; Bouillet, P; O'Donnell, K; Light, A; Tarlinton, DM; Strasser, A;
- Details
- Publication Year 2007-12-01,Volume 110,Issue #12,Page 3978-3984
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- Abstract
- T cell-dependent B-cell immune responses induce germinal centers that are sites for expansion, diversification, and selection of antigen-specific B cells. During the immune response, antigen-specific B cells are removed in a process that favors the retention of cells with improved affinity for antigen, a cell death process inhibited by excess Bcl-2. In this study, we examined the role of the BH3-only protein Bim, an initiator of apoptosis in the Bcl-2-regulated pathway, in the programmed cell death accompanying an immune response. After immunization, Bim-deficient mice showed persistence of both memory B cells lacking affinity-enhancing mutations in their immunoglobulin genes and antibody-forming cells secreting low-affinity antibodies. This was accompanied by enhanced survival of both cell types in culture. We have identified for the first time the physiologic mechanisms for killing low-affinity antibody-expressing B cells in an immune response and have shown this to be dependent on the BH3-only protein Bim.
- Publisher
- AMER SOC HEMATOLOGY
- Keywords
- BCL-2 FAMILY-MEMBER; IMMUNE-RESPONSE; APOPTOTIC RESPONSES; AFFINITY MATURATION; EXPRESSION; SELECTION; SURVIVAL; PUMA; NOXA; MICE
- Publisher's Version
- https://doi.org/10.1182/blood-2007-05-091306
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2007-12-01 12:00:00