Harless Smith Susan, Cancro Michael P
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Arch Immunol Ther Exp (Warsz). 2003;51(4):209-18.
The mechanisms that maintain a pool of B cells that is adequately diverse yet devoid of pathogenic autoreactivity remain poorly understood. 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. Since B lineage commitment is not coupled to peripheral B cell numbers and most mature peripheral B cells are quiescent, the sizes of mature peripheral compartments are primarily determined by the proportion of immature B cells that survive transit through later developmental stages, coupled with the longevity of mature B cells themselves. Compelling evidence indicates that the B cell antigen receptor (BcR) plays an essential role in all of these processes, but further findings indicate a similar role for the recently described tumor necrosis factor family member B lymphocyte stimulator (BLyS). Signaling through the BLyS receptor, Bcmd/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 striking congruence of BcR- and BLyS-mediated effects on B cell selection and survival suggests these pathways may be related. The recent discovery that BcR signaling is selectively coupled to Bcmd/BR3 expression links BcR- and BLyS-mediated activities in transitional and mature B cells, suggesting specificity-based selection and survival may be mechanistically similar processes.
维持一个具有足够多样性但缺乏致病性自身反应性的B细胞库的机制仍知之甚少。B细胞迁移到外周后完成成熟，在那里它们在被招募到长寿的初级库之前会经历几个中间发育阶段。由于B细胞谱系的确定与外周B细胞数量无关，并且大多数成熟的外周B细胞处于静止状态，成熟外周区室的大小主要由在后期发育阶段存活下来的未成熟B细胞的比例以及成熟B细胞自身的寿命决定。有力的证据表明，B细胞抗原受体（BcR）在所有这些过程中都起着至关重要的作用，但进一步的研究结果表明，最近描述的肿瘤坏死因子家族成员B淋巴细胞刺激因子（BLyS）也有类似作用。通过BLyS受体Bcmd/BR3发出的信号以两种方式控制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。BcR和BLyS介导的对B细胞选择和存活的影响惊人地一致，这表明这些途径可能有关联。最近发现BcR信号传导与Bcmd/BR3表达选择性偶联，这将过渡性和成熟B细胞中BcR和BLyS介导的活性联系起来，表明基于特异性的选择和存活可能是机制上相似的过程。
