Molecular pathways and mechanisms regulating the recombination of immunoglobulin genes during B-lymphocyte development.
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.
Johnson
Kristen
K
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
Reddy
Karen L
KL
Singh
Harinder
H
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D011995:Recombination, Genetic; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D014157:Transcription Factors