Article abstract
Nature Immunology 9, 396 - 404 (2008)
Published online: 24 February 2008 | doi:10.1038/ni1567
Association between the Igk and Igh immunoglobulin loci mediated by the 3' Igk enhancer induces 'decontraction' of the Igh locus in pre–B cells
Susannah L Hewitt1, Deborah Farmer2, Katarzyna Marszalek1, Emily Cadera3, Hong-Erh Liang3,5, Yang Xu4, Mark S Schlissel3 & Jane A Skok1,2
Abstract
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.
- Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.
- The Department of Immunology and Molecular Pathology, Division of Infection and Immunity, University College London, London W1T 4JF, UK.
- Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
- Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093, USA.
- Present address: University of California, San Francisco, San Francisco, California 94143, USA.
Correspondence to: Jane A Skok1,2 e-mail: jane.skok@med.nyu.edu