Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny
journal contributionposted on 2016-04-11, 00:00 authored by Satyendra Kumar, Robert Wuerffel, Ikbel Achour, Bryan Lajoie, Ranjan Sen, Job Dekker, Ann J Feeney, Amy L Kenter
V(D)J joining is mediated by RAG recombinase during early B-lymphocyte development in the bone marrow (BM). Activation-induced deaminase initiates isotype switching in mature B cells of secondary lymphoid structures. Previous studies questioned the strict ontological partitioning of these processes. We show that pro-B cells undergo robust switching to a subset of immunoglobulin H (IgH) isotypes. Chromatin studies reveal that in pro-B cells, the spatial organization of the Igh locus may restrict switching to this subset of isotypes. We demonstrate that in the BM, V(D)J joining and switching are interchangeably inducible, providing an explanation for the hyper-IgE phenotype of Omenn syndrome.
This work was supported by the National Institutes of Health (AI052400 to A.L.K., AI082918 to A.J.F., and HG003143 and HG00459 to J.D), the W.M. Keck Foundation (to J.D), and the Intramural Research Program of the National Institute on Aging (Baltimore, MD) (to R.S.).
PublisherCold Spring Harbor Laboratory Press