Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny

Satyendra Kumar, Robert Wuerffel, Ikbel Achour, Bryan Lajoie, Ranjan Sen, Job Dekker, Ann J. Feeney, Amy L. Kenter

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2439-2444
Number of pages6
JournalGenes & development
Volume27
Issue number22
DOIs
StatePublished - Nov 15 2013
Externally publishedYes

Keywords

  • Ag gene rearrangement
  • B-cell development
  • Gene expression

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny'. Together they form a unique fingerprint.

  • Cite this

    Kumar, S., Wuerffel, R., Achour, I., Lajoie, B., Sen, R., Dekker, J., Feeney, A. J., & Kenter, A. L. (2013). Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny. Genes & development, 27(22), 2439-2444. https://doi.org/10.1101/gad.227165.113