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

Immunol Rev. 2004 Feb:197:89-101. doi: 10.1111/j.0105-2896.2004.0099.x.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Cell Differentiation
  • Cell Lineage
  • Homeostasis
  • Mice
  • Models, Immunological
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Signal Transduction

Substances

  • BLyS receptor
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, B-Cell
  • Receptors, Tumor Necrosis Factor
  • Bcl2 protein, mouse