Open AccessClonally stable Vκ allelic choice instructs Igκ repertoire
Author(s) -
Rena LevinKlein,
Shira Fraenkel,
Michal Lichtenstein,
Louise S. Matheson,
Osnat Bartok,
Yuval Nevo,
Sebastián Kadener,
Anne E. Corcoran,
Howard Cedar,
Yehudit Bergman
Publication year - 2017
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms15575
Subject(s) - repertoire , allele , genetics , biology , evolutionary biology , computational biology , gene , physics , acoustics
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.