Through a glass less darkly: apoptosis and the germinal center response to antigen
- Author(s)
- Peperzak, V; Vikstrom, IB; Tarlinton, DM;
- Journal Title
- IMMUNOLOGICAL REVIEWS
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- WILEY-BLACKWELL
- Keywords
- MEMORY B-CELLS; FOLLICULAR DENDRITIC CELLS; MULTIPLE-MYELOMA CELLS; SINGLE-STRANDED-DNA; V-REGION GENES; IMMUNOGLOBULIN-SECRETING CELLS; ANTIBODY-FORMING-CELLS; BCL-2 INHIBITOR HA14-1; BH3 MIMETIC ABT-737; SOMATIC HYPERMUTATION
- Research Division(s)
- Immunology
- Publisher's Version
- https://doi.org/10.1111/j.1600-065X.2012.01123.x
- Terms of Use/Rights Notice
- © 2012 John Wiley & Sons A/S
Creation Date: 2012-05-01 12:00:00