Basal B-cell receptor signaling in B lymphocytes: mechanisms of regulation and role in positive selection, differentiation, and peripheral survival |
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Authors: | Ezequiel M Fuentes-Pananá Gregory Bannish John G Monroe |
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Institution: | Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. |
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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. |
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