Reversible contraction by looping of the Tcra and Tcrb loci in rearranging thymocytes.
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.
Skok
Jane A
JA
Department of Immunology and Molecular Pathology, Division of Infection and Immunity, University College London, London W1T 4JF, UK.
Gisler
Ramiro
R
Novatchkova
Maria
M
Farmer
Deborah
D
de Laat
Wouter
W
Busslinger
Meinrad
M
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000276:immunology; D015329:Gene Rearrangement, T-Lymphocyte / Q000276:immunology*; D019673:Genes, T-Cell Receptor alpha / Q000276:immunology*; D019674:Genes, T-Cell Receptor beta / Q000276:immunology*; D019676:Genes, T-Cell Receptor delta / Q000276:immunology*; D007127:Immunoglobulin Constant Regions / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D017404:In Situ Hybridization, Fluorescence; D038041:Lymphopoiesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D051757:PAX5 Transcription Factor / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D004268:DNA-Binding Proteins; D007127:Immunoglobulin Constant Regions; D007135:Immunoglobulin Variable Region; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C499308:Rag2 protein, mouse