Integrating B cell homeostasis and selection with BLyS.
Integrating B cell homeostasis and selection with BLyS.
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DOI：
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发表时间：
2003
影响因子：
3.2
通讯作者：
Susan Harless Smith;M. Cancro
中科院分区：
文献类型：
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作者：
Susan Harless Smith;M. Cancro
维持B细胞库足够多样化但缺乏致病性自身反应性的机制仍然知之甚少。B细胞在迁移到外周后完成成熟，在那里它们在募集到长寿命的原代池之前经过几个中间发育阶段。由于B谱系定型与外周B细胞数量无关，并且大多数成熟的外周B细胞是静止的，因此成熟外周区室的大小主要由存活通过后期发育阶段的未成熟B细胞的比例以及成熟B细胞本身的寿命决定。令人信服的证据表明，B细胞抗原受体（BcR）在所有这些过程中发挥了重要作用，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）的类似作用。通过BLyS受体Bcmd/BR 3的信号传导以两种方式控制B细胞数量：通过改变完成过渡期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介导的效应对B细胞选择和存活的显著一致性表明这些途径可能是相关的。最近发现BcR信号选择性地与Bcmd/BR 3表达偶联，这将过渡期和成熟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械上相似的过程。
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.