Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells
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
Rights Notice
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Creation Date: 2007-12-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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