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Initiation of allelic exclusion by stochastic interaction of Tcrb alleles with repressive nuclear compartments.

Publication ,  Journal Article
Schlimgen, RJ; Reddy, KL; Singh, H; Krangel, MS
Published in: Nat Immunol
July 2008

Studies of antigen-receptor loci have linked directed monoallelic association with pericentromeric heterochromatin to the initiation or maintenance of allelic exclusion. Here we provide evidence for a fundamentally different basis for T cell antigen receptor-beta (Tcrb) allelic exclusion. Using three-dimensional immunofluorescence in situ hybridization, we found that germline Tcrb alleles associated stochastically and at high frequency with the nuclear lamina or with pericentromeric heterochromatin in developing thymocytes and that such interactions inhibited variable-to-diversity-joining (V(beta)-to-D(beta)J(beta)) recombination before beta-selection. The introduction of an ectopic enhancer into Tcrb resulted in fewer such interactions and impaired allelic exclusion. We propose that initial V(beta)-to-D(beta)J(beta) recombination events are generally monoallelic in developing thymocytes because of frequent stochastic, rather than directed, interactions of Tcrb alleles with repressive nuclear compartments. Such interactions may be essential for Tcrb allelic exclusion.

Duke Scholars

Published In

Nat Immunol

DOI

EISSN

1529-2916

Publication Date

July 2008

Volume

9

Issue

7

Start / End Page

802 / 809

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Receptors, Antigen, T-Cell, alpha-beta
  • Microscopy, Confocal
  • Mice, Transgenic
  • Mice
  • Immunology
  • Genes, T-Cell Receptor beta
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Cell Nucleus
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Schlimgen, R. J., Reddy, K. L., Singh, H., & Krangel, M. S. (2008). Initiation of allelic exclusion by stochastic interaction of Tcrb alleles with repressive nuclear compartments. Nat Immunol, 9(7), 802–809. https://doi.org/10.1038/ni.1624
Schlimgen, Ryan J., Karen L. Reddy, Harinder Singh, and Michael S. Krangel. “Initiation of allelic exclusion by stochastic interaction of Tcrb alleles with repressive nuclear compartments.Nat Immunol 9, no. 7 (July 2008): 802–9. https://doi.org/10.1038/ni.1624.
Schlimgen RJ, Reddy KL, Singh H, Krangel MS. Initiation of allelic exclusion by stochastic interaction of Tcrb alleles with repressive nuclear compartments. Nat Immunol. 2008 Jul;9(7):802–9.
Schlimgen, Ryan J., et al. “Initiation of allelic exclusion by stochastic interaction of Tcrb alleles with repressive nuclear compartments.Nat Immunol, vol. 9, no. 7, July 2008, pp. 802–09. Pubmed, doi:10.1038/ni.1624.
Schlimgen RJ, Reddy KL, Singh H, Krangel MS. Initiation of allelic exclusion by stochastic interaction of Tcrb alleles with repressive nuclear compartments. Nat Immunol. 2008 Jul;9(7):802–809.

Published In

Nat Immunol

DOI

EISSN

1529-2916

Publication Date

July 2008

Volume

9

Issue

7

Start / End Page

802 / 809

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Receptors, Antigen, T-Cell, alpha-beta
  • Microscopy, Confocal
  • Mice, Transgenic
  • Mice
  • Immunology
  • Genes, T-Cell Receptor beta
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Cell Nucleus