UMMS Affiliation

Programs in Systems Biology; Department of Biochemistry and Molecular Pharmacology

Publication Date

2013-11-15

Document Type

Article

Disciplines

Developmental Biology | Genetics and Genomics | Systems Biology

Abstract

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.

Keywords

B-cell development, Ag gene rearrangement, Gene expression

DOI of Published Version

10.1101/gad.227165.113

Source

Kumar S, Wuerffel R, Achour I, Lajoie B, Sen R, Dekker J, Feeney AJ, Kenter AL. Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny. Genes Dev. 2013 Nov 15;27(22):2439-44. doi: 10.1101/gad.227165.113. Link to article on publisher's site

Journal/Book/Conference Title

Genes and development

Comments

© 2013 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.

Related Resources

Link to Article in PubMed

PubMed ID

24240234

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