Cancro Michael P
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082, USA.
Immunol Rev. 2004 Feb;197:89-101. doi: 10.1111/j.0105-2896.2004.0099.x.
B cells complete maturation after migrating to the periphery, where they transit several intermediate developmental stages prior to recruitment into the long-lived primary pool. Because B-lineage commitment is not regulated by peripheral pool size and most peripheral B cells are quiescent, the primary factors governing steady-state numbers are the proportion of immature B cells surviving transit through later developmental stages and the longevity of mature B cells themselves. Substantial evidence indicates that the B-cell receptor (BCR) plays an essential role in all these processes, but recent findings suggest a central role for the recently described tumor necrosis factor (TNF) family member, B-lymphocyte stimulator (BLyS). Signaling through one of the BLyS receptors, BLyS receptor 3 (BR3), controls B-cell numbers in two ways: by varying the proportion of cells that complete transitional B-cell development and by serving as the primary determinant of mature B-cell longevity. The recent discovery that BCR signaling is selectively coupled to BR3 expression in a developmentally regulated fashion links BCR- and BLyS-mediated events, suggesting that specificity-based selection and survival may be mechanistically similar processes.
B细胞迁移至外周后完成成熟，在外周，它们在被招募进入长寿的初级库之前会经历几个中间发育阶段。由于B细胞系的定向分化不受外周库大小的调节，并且大多数外周B细胞处于静止状态，因此决定稳态数量的主要因素是未成熟B细胞在经历后续发育阶段后存活的比例以及成熟B细胞自身的寿命。大量证据表明，B细胞受体（BCR）在所有这些过程中都起着至关重要的作用，但最近的研究结果表明，最近描述的肿瘤坏死因子（TNF）家族成员B淋巴细胞刺激因子（BLyS）也发挥着核心作用。通过BLyS受体之一BLyS受体3（BR3）进行的信号传导以两种方式控制B细胞数量：通过改变完成过渡性B细胞发育的细胞比例以及作为成熟B细胞寿命的主要决定因素。最近发现BCR信号传导以发育调节的方式选择性地与BR3表达偶联，这将BCR和BLyS介导的事件联系起来，表明基于特异性的选择和存活可能是机制上相似的过程。
