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PMID: 9034140 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Changes in locus-specific V(D)J recombinase activity induced by immunoglobulin gene products during B cell development.

The Journal of experimental medicine ·Vol. 185 ·No. 4 ·1997-02-17 ·Pages 609-20

Constantinescu A, Schlissel MS

Abstract

The process of V(D)J recombination is crucial for regulating the development of B cells and for determining their eventual antigen specificity. Here we assess the developmental regulation of the V(D)J recombinase directly, by monitoring the double-stranded DNA breaks produced in the process of V(D)J recombination. This analysis provides a measure of recombinase activity at immunoglobulin heavy and light chain loci across defined developmental stages spanning the process of B cell development. We find that expression of a complete immunoglobulin heavy chain protein is accompanied by a drastic change in the targeting of V(D)J recombinase activity, from being predominantly active at the heavy chain locus in pro-B cells to being exclusively restricted to the light chain loci in pre-B cells. This switch in locus-specific recombinase activity results in allelic exclusion at the immunoglobulin heavy chain locus. Allelic exclusion is maintained by a different mechanism at the light chain locus. We find that immature, but not mature, B cells that already express a functional light chain protein can undergo continued light chain gene rearrangement, by replacement of the original rearrangement on the same allele. Finally, we find that the developmentally regulated targeting of V(D)J recombination is unaffected by enforced rapid transit through the cell cycle induced by an E mu-myc transgene.

MeSH Terms
Animals B-Lymphocytes/cytology,enzymology,immunology DNA/metabolism DNA Damage DNA Nucleotidyltransferases/metabolism Female Genes, Immunoglobulin Immunoglobulin G/genetics,immunology Immunoglobulin M/genetics,immunology Mice Mice, Inbred BALB C VDJ Recombinases
Chemicals
Immunoglobulin G Immunoglobulin M DNA DNA Nucleotidyltransferases VDJ Recombinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Constantinescu A
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Schlissel M S
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.185.4.609
Published
1997-02-17
Pages
609-20
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2196138
Subset
IM
Grants
NIGMS NIH HHS · GM07309 · United States
NHLBI NIH HHS · R01 HL48702 · United States
External Links
PubMed source DOI: 10.1084/jem.185.4.609 PMC Full Text View journal details
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