Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci

Magdalena B. Rother, Robert Jan Palstra, Suchit Jhunjhunwala, Kevin A. M. van Kester, Wilfred F. J. van IJcken, Rudi W. Hendriks, Jacques J. M. van Dongen, Cornelis Murre, Menno C. van Zelm

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Progenitor-B cells recombine their immunoglobulin (Ig) loci to create unique antigen receptors. Despite a common recombination machinery, the Ig heavy and Ig light chain loci rearrange in a stepwise manner. We studied pre-pro-B cells and Rag-/- progenitor-B cells to determine whether Ig locus contraction or nuclear positioning is decisive for stepwise rearrangements. We found that both Ig loci were contracted in pro-B and pre-B cells. Igh relocated from the nuclear lamina to central domains only at the pro-B cell stage, whereas, Igk remained sequestered at the lamina, and only at the pre-B cell stage located to central nuclear domains. Finally, in vitro induced re-positioning of Ig alleles away from the nuclear periphery increased germline transcription of Ig loci in pre-pro-B cells. Thus, Ig locus contraction juxtaposes genomically distant elements to mediate efficient recombination, however, sequential positioning of Ig loci away from the nuclear periphery determines stage-specific accessibility of Ig loci.

Original languageEnglish
Pages (from-to)175-186
Number of pages12
JournalNucleic Acids Research
Volume44
Issue number1
DOIs
Publication statusPublished - 8 Jan 2016
Externally publishedYes

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