Immature B cells preferentially switch to IgE with increased direct Sμ to Sε recombination

Duane R. Wesemann, Jennifer M. Magee, Cristian Boboila, Dinis Pedro Calado, Michael P. Gallagher, Andrew J. Portuguese, John P. Manis, Xiaolong Zhou, Mike Recher, Klaus Rajewsky, Luigi D. Notarangelo, Frederick W. Alt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces initially expressed Cμ (IgM) constant regions (C H) exons with downstream C H exons. Stimulation of B cells with anti-CD40 plus interleukin-4 induces CSR from Cμ to Cγ1 (IgG1) and Cε (IgE), the latter of which contributes to the pathogenesis of atopic diseases. Although Cε CSR can occur directly from Cμ, most mature peripheral B cells undergo CSR to Cε indirectly, namely from Cμ to Cγ1, and subsequently to Cε. Physiological mechanisms that influence CSR to Cγ1 versus Cε are incompletely understood. In this study, we report a role for B cell developmental maturity in IgE CSR. Based in part on a novel flow cytometric IgE CSR assay, we show that immature B cells preferentially switch to IgE versus IgG1 through a mechanism involving increased direct CSR from Cμ to Cε. Our findings suggest that IgE dysregulation in certain immunodeficiencies may be related to impaired B cell maturation.

Original languageEnglish (US)
Pages (from-to)2733-2746
Number of pages14
JournalJournal of Experimental Medicine
Volume208
Issue number13
DOIs
StatePublished - Dec 19 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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