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.

1. Department of Immunology and Molecular Pathology, Division of Infection and Immunity, University College London, London W1T 4JF, UK.
2. Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria.
3. Department of Cell Biology and Genetics, Erasmus Medical Centre, 3000 CA Rotterdam, The Netherlands.
4. Present address: Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.
5. These authors contributed equally to this work.

Correspondence to: Ramiro Gisler^2,5 e-mail: busslinger@imp.univie.ac.at

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