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Adv Exp Med Biol. 2009;650:133-47.

Molecular pathways and mechanisms regulating the recombination of immunoglobulin genes during B-lymphocyte development.

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1
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.

Abstract

The hallmark of B-cell development is the ordered recombination of immunoglobulin (Ig) genes. Recently, considerable progress has been achieved in assembling gene regulatory networks comprised of signaling components and transcription factors that regulate B-cell development. In this chapter we synthesize experimental evidence to explain how such signaling pathways and transcription factors can orchestrate the ordered recombination of immunoglobulin (Ig) genes. Recombination of antigen-receptor loci is regulated both by the developmentally controlled expression of the Rag1 and Rag2 genes and the accessibility of particular loci and their gene segments to recombination. A new framework has emerged that invokes nuclear compartmentalization, large-scale chromatin dynamics and localized changes in chromatin structure in regulating the accessibility of Ig loci at specific stages of B-cell development. We review this emergent framework and discuss new experimental approaches that will be needed to explore the underlying molecular mechanisms.

PMID:
19731807
[Indexed for MEDLINE]

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