Author:
Sayegh Camil,Jhunjhunwala Suchit,Riblet Roy,Murre Cornelis
Abstract
The immunoglobulin heavy-chain (IgH) locus undergoes large-scale contraction in B cells poised to undergo IgH V(D)J recombination. We considered the possibility that looping of distinct IgH V regions plays a role in promoting long-range interactions. Here, we simultaneously visualize three subregions of the IgH locus, using three-dimensional fluorescence in situ hybridization. Looping within the IgH locus was observed in both B- and T-lineage cells. However, monoallelic looping of IgH V regions into close proximity of the IgH DJ cluster was detected in developing B cells with significantly higher frequency when compared with hematopoietic progenitor or CD8+ T-lineage cells. Looping of a subset of IgH V regions, albeit at lower frequency, was also observed in RAG-deficient pro-B cells. Based on these observations, we propose that Ig loci are repositioned by a looping mechanism prior to IgH V(D)J rearrangement to facilitate the joining of Ig variable, diversity, and joining segments.
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
164 articles.
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