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, Igê 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.,
Nucleic Acids Research
Department of Immunology

Rother, M., Palstra, R.-J., Jhunjhunwala, S., Van Kester, K. A. M., van IJcken, W., Hendriks, R., … van Zelm, M. (2016). Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci. Nucleic Acids Research, 44(1), 175–186. doi:10.1093/nar/gkv928