Positive selection and lineage commitment during peripheral B-lymphocyte development

Immunol Rev. 2004 Feb;197:206-18. doi: 10.1111/j.0105-2896.2003.097.x.

Abstract

Although it is appreciated that the antigen receptor on B cells is required for peripheral B-lymphocyte development and survival, it has been unclear whether this receptor interacts with self-antigens during development or if it signals constitutively in an antigen-independent fashion. The analysis of mutant mice in which antigen receptor signaling in B cells is either attenuated or enhanced has revealed the existence of a follicular versus marginal zone B-lymphocyte cell-fate decision. These analyses indicate that weak antigen receptor-derived signals favor marginal zone B-cell generation, and relatively strong signals favor the development of mature follicular B cells. Even stronger signals derived from the antigen receptor favor the generation of B1 B cells. This signal strength model for B-cell development supports the notion that self-antigens of varying affinity may mediate positive selection and lineage commitment. Direct evidence supporting such a view has been obtained from the analysis of antigen receptor knockin mice. Specific antigen receptors guide B cells to develop into specific lineages. Although Notch-2, nuclear factor-kappaBp50, and other genes are essential for marginal zone B-cell development, instructive signals delivered by the antigen receptor represent the primary force driving positive selection and lineage commitment in B lymphocytes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology*
  • Cell Lineage
  • Humans
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / immunology
  • Mice
  • NF-kappa B / physiology
  • NF-kappa B p50 Subunit
  • Receptor, Notch2
  • Receptors, Antigen, B-Cell / physiology
  • Receptors, Cell Surface / physiology
  • Signal Transduction
  • Spleen / cytology
  • Spleen / immunology

Substances

  • NF-kappa B
  • NF-kappa B p50 Subunit
  • NOTCH2 protein, human
  • Notch2 protein, mouse
  • Receptor, Notch2
  • Receptors, Antigen, B-Cell
  • Receptors, Cell Surface