Positive selection and lineage commitment during peripheral B‐lymphocyte development

Summary:  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‐κBp50, 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.

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