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

Academic Article
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Overview

authors

  • Kumar, S.
  • Wuerffel, R.
  • Achour, I.
  • Lajoie, B.
  • Sen, R.
  • Dekker, J.
  • Feeney, Ann
  • Kenter, A. L.

publication date

  • November 2013

journal

  • Genes & Development  Journal

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.

subject areas

  • Animals
  • B-Lymphocytes
  • Cell Differentiation
  • Cell Line
  • Cells, Cultured
  • Gene Expression Regulation, Developmental
  • Immunoglobulin Isotypes
  • Mice
  • Precursor Cells, B-Lymphoid
  • VDJ Exons
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Research

keywords

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

PubMed Central ID

  • PMC3841733

International Standard Serial Number (ISSN)

  • 0890-9369

Digital Object Identifier (DOI)

  • 10.1101/gad.227165.113

PubMed ID

  • 24240234
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Additional Document Info

start page

  • 2439

end page

  • 2444

volume

  • 27

issue

  • 22

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