Association between the Igk and Igh immunoglobulin loci mediated by the 3′ Igk enhancer induces 'decontraction' of the Igh locus in pre-B cells

被引：59

作者：

Hewitt, Susannah L. ^{[1
]}

Farmer, Deborah ^{[2
]}

Marszalek, Katarzyna ^{[1
]}

Cadera, Emily ^{[3
]}

Liang, Hong-Erh ^{[3
]}

Xu, Yang ^{[4
]}

Schlissel, Mark S. ^{[3
]}

Skok, Jane A. ^{[1
,2
]}

机构：

[1] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[2] UCL, Dept Immunol & Mol Pathol, Div Infect Immun, London W1T 4JF, England

[3] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[4] Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 04期

基金：

英国惠康基金;

关键词：

D O I：

10.1038/ni1567

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Variable-(diversity)-joining (V(D)J) recombination at loci encoding the immunoglobulin heavy chain (Igh) and immunoglobulin light chain (Igk) takes place sequentially during successive stages in B cell development. Using three-dimensional DNA fluorescence in situ hybridization, here we identify a lineage-specific and stage-specific interchromosomal association between these two loci that marks the transition between Igh and Igk recombination. Colocalization occurred 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 greater distal rearrangement of the gene encoding the variable heavy-chain region. Our data indicate involvement of the Igk locus and its 3' enhancer in directing the Igh locus to a repressive nuclear subcompartment and inducing the Igh locus to decontract.

引用

页码：396 / 404

页数：9

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