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 alpha delta ( 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.