Reversible contraction by looping of the Tcra and Tcrb loci in rearranging thymocytes

Nat Immunol. 2007 Apr;8(4):378-87. doi: 10.1038/ni1448. Epub 2007 Mar 4.

Abstract

Reversible contraction of immunoglobulin loci juxtaposes the variable (V) genes next to the (diversity)-joining-constant ((D)JC) gene domain, thus facilitating V-(D)J recombination. Here we show that the T cell receptor beta (Tcrb) and T cell receptor alphadelta (Tcra-Tcrd) loci also underwent long-range interactions by looping in double-negative and double-positive thymocytes, respectively. Contraction of the Tcrb and Tcra loci occurred in rearranging thymocytes and was reversed at the next developmental stage. Decontraction of the Tcrb locus probably prevented further V(beta)-DJ(beta) rearrangements in double-positive thymocytes by separating the V(beta) genes from the DJC(beta) domain. In most double-negative cells, one Tcrb allele was recruited to pericentromeric heterochromatin. Such allelic positioning may facilitate asynchronous V(beta)-DJ(beta) recombination. Hence, pericentromeric recruitment and locus 'decontraction' seem to contribute to the initiation and maintenance of allelic exclusion at the Tcrb locus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • DNA-Binding Proteins / immunology
  • Gene Rearrangement, T-Lymphocyte / immunology*
  • Genes, T-Cell Receptor alpha / immunology*
  • Genes, T-Cell Receptor beta / immunology*
  • Genes, T-Cell Receptor delta / immunology*
  • Immunoglobulin Constant Regions / immunology
  • Immunoglobulin Variable Region / immunology
  • In Situ Hybridization, Fluorescence
  • Lymphopoiesis / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Confocal
  • PAX5 Transcription Factor / immunology
  • T-Lymphocytes / immunology*

Substances

  • DNA-Binding Proteins
  • Immunoglobulin Constant Regions
  • Immunoglobulin Variable Region
  • PAX5 Transcription Factor
  • Pax5 protein, mouse
  • Rag2 protein, mouse