Clonally stable Vκ allelic choice instructs Igκ repertoire

Rena Levin-Klein, Shira Fraenkel, Michal Lichtenstein, Louise S. Matheson, Osnat Bartok, Yuval Nevo, Sebastian Kadener, Anne E. Corcoran, Howard Cedar and Yehudit Bergman ()
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Rena Levin-Klein: Institute for Medical Research Israel–Canada, Hebrew University Medical School
Shira Fraenkel: Institute for Medical Research Israel–Canada, Hebrew University Medical School
Michal Lichtenstein: Institute for Medical Research Israel–Canada, Hebrew University Medical School
Louise S. Matheson: Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus
Osnat Bartok: Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University
Yuval Nevo: Computation Center, Hebrew University–Hadassah Medical School
Sebastian Kadener: Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University
Anne E. Corcoran: Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus
Howard Cedar: Institute for Medical Research Israel–Canada, Hebrew University Medical School
Yehudit Bergman: Institute for Medical Research Israel–Canada, Hebrew University Medical School

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract Although much has been done to understand how rearrangement of the Igκ locus is regulated during B-cell development, little is known about the way the variable (V) segments themselves are selected. Here we show, using B6/Cast hybrid pre-B-cell clones, that a limited number of V segments on each allele is stochastically activated as characterized by the appearance of non-coding RNA and histone modifications. The activation states are clonally distinct, stable across cell division and developmentally important in directing the Ig repertoire upon differentiation. Using a new approach of allelic ATAC-seq, we demonstrate that the Igκ V alleles have differential chromatin accessibility, which may serve as the underlying basis of clonal maintenance at this locus, as well as other instances of monoallelic expression throughout the genome. These findings highlight a new level of immune system regulation that optimizes gene diversity.

Date: 2017
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DOI: 10.1038/ncomms15575

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