Skok Jane A, Gisler Ramiro, Novatchkova Maria, Farmer Deborah, de Laat Wouter, Busslinger Meinrad
Department of Immunology and Molecular Pathology, Division of Infection and Immunity, University College London, London W1T 4JF, UK.
Nat Immunol. 2007 Apr;8(4):378-87. doi: 10.1038/ni1448. Epub 2007 Mar 4.
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.
免疫球蛋白基因座的可逆收缩使可变（V）基因与（多样性）连接恒定（（D）JC）基因结构域相邻，从而促进V-（D）J重组。我们在此表明，T细胞受体β（Tcrb）和T细胞受体αδ（Tcra-Tcrd）基因座也分别通过在双阴性和双阳性胸腺细胞中形成环而发生长程相互作用。Tcrb和Tcra基因座的收缩发生在正在重排的胸腺细胞中，并在下一个发育阶段逆转。Tcrb基因座的解收缩可能通过将Vβ基因与DJCβ结构域分离，阻止双阳性胸腺细胞中进一步的Vβ-DJβ重排。在大多数双阴性细胞中，一个Tcrb等位基因被募集到着丝粒周围异染色质。这种等位基因定位可能促进异步Vβ-DJβ重组。因此，着丝粒周围募集和基因座“解收缩”似乎有助于Tcrb基因座等位基因排斥的启动和维持。
