Article abstract
Nature Immunology 8, 378 - 387 (2007)
Published online: 4 March 2007 | doi:10.1038/ni1448
Reversible contraction by looping of the Tcra and Tcrb loci in rearranging thymocytes
Jane A Skok1,4,5, Ramiro Gisler2,5, Maria Novatchkova2, Deborah Farmer1, Wouter de Laat3 & Meinrad Busslinger2
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 
(Tcrb) and T cell receptor 
(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
-DJ rearrangements in double-positive thymocytes by separating the V genes from the DJC domain. In most double-negative cells, one Tcrb allele was recruited to pericentromeric heterochromatin. Such allelic positioning may facilitate asynchronous V-DJ recombination. Hence, pericentromeric recruitment and locus 'decontraction' seem to contribute to the initiation and maintenance of allelic exclusion at the Tcrb locus.
- Department of Immunology and Molecular Pathology, Division of Infection and Immunity, University College London, London W1T 4JF, UK.
- Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria.
- Department of Cell Biology and Genetics, Erasmus Medical Centre, 3000 CA Rotterdam, The Netherlands.
- Present address: Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.
- These authors contributed equally to this work.
Correspondence to: Ramiro Gisler2,5 e-mail: busslinger@imp.univie.ac.at
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