Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny
journal contributionposted on 11.04.2016 by Satyendra Kumar, Robert Wuerffel, Ikbel Achour, Bryan Lajoie, Ranjan Sen, Job Dekker, Ann J Feeney, Amy L Kenter
Any type of content formally published in an academic journal, usually following a peer-review process.
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.