Peripheral B‐cell maturation: the intersection of selection and homeostasis

MP Cancro - Immunological reviews, 2004 - Wiley Online Library
Immunological reviews, 2004Wiley Online Library
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 …
Summary
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.
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