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

• Published in: The Journal of experimental medicine Vol. 208; no. 13; pp. 2733 - 2746
• Main Authors: Wesemann, Duane R, Magee, Jennifer M, Boboila, Cristian, Calado, Dinis Pedro, Gallagher, Michael P, Portuguese, Andrew J, Manis, John P, Zhou, Xiaolong, Recher, Mike, Rajewsky, Klaus, Notarangelo, Luigi D, Alt, Frederick W
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 19.12.2011
• Subjects: Animals; B-Lymphocytes - immunology; Common Variable Immunodeficiency - genetics; Common Variable Immunodeficiency - immunology; Immunoglobulin Class Switching - physiology; Immunoglobulin E - genetics; Immunoglobulin E - immunology; Immunoglobulin epsilon-Chains - genetics; Immunoglobulin epsilon-Chains - immunology; Immunoglobulin G - genetics; Immunoglobulin G - immunology; Immunoglobulin mu-Chains - genetics; Immunoglobulin mu-Chains - immunology; Mice; Mice, Knockout; Recombination, Genetic - physiology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20111155

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.