Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells

Silke F. Fischer, Philippe Bouillet, Kristy O'Donnell, Amanda Light, David M. Tarlinton, Andreas Strasser

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78 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3978-3984
Number of pages7
JournalBlood
Volume110
Issue number12
DOIs
Publication statusPublished - 1 Dec 2007

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