Basal B‐cell receptor signaling in B lymphocytes: mechanisms of regulation and role in positive selection, differentiation, and peripheral survival

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Abstract
Summary: B‐cell development is a highly ordered multistep process dependent upon signals generated by the pre‐B and B‐cell antigen receptor (BCR). BCR signals drive maturation of the B cell by integrating a number of parallel and sequential biological processes that result in generation of fully immunocompetent B cells. Among these biological processes are positive selection through several developmental checkpoints, negative selection of potentially self‐reactive B cells, and activation of the mature B cell. In addition, recent studies have shown that developing and mature B cells rely on the constant activity of the BCR for their continued survival. Ligand (antigen)‐dependent and ‐independent mechanisms of BCR signaling have been proposed, but their specific contributions to B‐cell maturation and differentiation in the bone marrow and periphery are not completely clear. We discuss here a model, whereby ligand‐independent basal BCR activity would be sufficient to trigger B‐cell development through to the mature stage. However, long‐term survival and formation of specific mature B‐cell populations may be dependent on ligand–receptor interactions.