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Biochem J. 2019 Mar 6;476(5):769-778. doi: 10.1042/BCJ20180565.

Signalling circuits that direct early B-cell development.

Author information

1
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, U.K. Georg.Petkau@babraham.ac.uk.
2
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, U.K.

Abstract

In mammals, the B-cell lineage arises from pluripotent progenitors in the bone marrow. During their development, B-cells undergo lineage specification and commitment, followed by expansion and selection. These processes are mediated by regulated changes in gene expression programmes, rearrangements of immunoglobulin (Ig) genes, and well-timed rounds of proliferation and apoptosis. Many of these processes are initiated by environmental factors including cytokines, chemokines, and cell-cell contacts. Developing B-cells process these environmental cues into stage-specific functions via signalling pathways including the PI3K, MAPK, or JAK-STAT pathway. The cytokines FLT3-Ligand and c-Kit-Ligand are important for the early expansion of the B-cell precursors at different developmental stages and conditions. Interleukin 7 is essential for commitment to the B-cell lineage and for orchestrating the Ig recombination machinery. After rearrangement of the immunoglobulin heavy chain, proliferation and apoptosis, and thus selection, are mediated by the clonal pre-B-cell receptor, and, following light chain rearrangement, by the B-cell receptor.

KEYWORDS:

B-lymphocyte development; FLT3L; IL7; c-Kit; lineage commitment; signalling

PMID:
30842310
DOI:
10.1042/BCJ20180565

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