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Through a glass less darkly: apoptosis and the germinal center response to antigen
Author(s) -
Peperzak Victor,
Vikstrom Ingela B.,
Tarlinton David M.
Publication year - 2012
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2012.01123.x
Subject(s) - germinal center , biology , immune system , apoptosis , microbiology and biotechnology , antigen , programmed cell death , immunology , transgene , b cell , genetics , antibody , gene
Summary: The regulation of cell death is crucial for normal immune responses. Apoptosis is required for appropriate affinity‐based recruitment of B cells into an immune response, for the normal expansion, contraction – and thereby selection – of B cells within germinal centers, and also for the normal expansion, contraction, and persistence of plasma cells, both extrafollicular and germinal center‐derived. In this review, we focus on the intrinsic pathway of apoptosis, which is mediated by the interaction of pro‐ and anti‐apoptotic members of the Bcl‐2 family of proteins. Early, relatively crude studies using transgene‐mediated over‐expression of pro‐survival proteins or germline‐encoded loss of pro‐apoptotic proteins demonstrated clearly the consequences of dysregulation of this apoptosis pathway on immunity. More recent studies have both been more targeted and extensive, meaning that a large number of Bcl‐2 family members have been assessed for roles in immune regulation in a relatively precise manner. These studies are revealing a level of specialization in the use of the pro‐survival proteins during immune responses, with several showing what appear to be stage‐specific contributions. Lastly, we consider the involvement of Bcl‐2 family proteins in the transformation of B cells at distinct stages of the response to antigen, comparing this involvement with that in the normal processes.