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Nat Commun. 2017 May 30;8:15575. doi: 10.1038/ncomms15575.

Clonally stable Vκ allelic choice instructs Igκ repertoire.

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Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University Medical School, Jerusalem 91120, Israel.
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
Biological Chemistry Department, Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.
Computation Center, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.


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.

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