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.
V(D)J recombination at Igh and Igk loci takes place sequentially during successive stages in B cell development. Using 3-dimensional DNA fluorescence in situ hybridization (FISH), we identified a lineage-and stage-specific interchromosomal association between these two loci which marks the transition between Igh and Igk recombination. Co-localization occured between pericentromerically located alleles in pre-B cells, and was mediated by the 3' Igk enhancer. Deletion of this regulatory element prevented association of the Igh and Igk loci, inhibited pericentromeric recruitment and locus decontraction of an Igh allele, and resulted in increased distal V H gene rearrangement. Our data indicate a role for the Igk locus and its 3' enhancer in directing the Igh locus to a repressive nuclear subcompartment, and in rendering the Igh locus unable to contract.
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