First Author | Wesemann DR | Year | 2011 |
Journal | J Exp Med | Volume | 208 |
Issue | 13 | Pages | 2733-46 |
PubMed ID | 22143888 | Mgi Jnum | J:179049 |
Mgi Id | MGI:5301014 | Doi | 10.1084/jem.20111155 |
Citation | Wesemann DR, et al. (2011) Immature B cells preferentially switch to IgE with increased direct Smu to S{varepsilon} recombination. J Exp Med 208(13):2733-46 |
abstractText | Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces initially expressed Cmu (IgM) constant regions (C(H)) exons with downstream C(H) exons. Stimulation of B cells with anti-CD40 plus interleukin-4 induces CSR from Cmu to Cgamma1 (IgG1) and Cepsilon (IgE), the latter of which contributes to the pathogenesis of atopic diseases. Although Cepsilon CSR can occur directly from Cmu, most mature peripheral B cells undergo CSR to Cepsilon indirectly, namely from Cmu to Cgamma1, and subsequently to Cepsilon. Physiological mechanisms that influence CSR to Cgamma1 versus Cepsilon 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 Cmu to Cepsilon. Our findings suggest that IgE dysregulation in certain immunodeficiencies may be related to impaired B cell maturation. |