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

Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces initially expressed C mu (IgM) constant regions (C(H)) exons with downstream C(H) exons. Stimulation of B cells with anti-CD40 plus interleukin-4 induces CSR from C mu to C gamma 1 (IgG1) and C epsilon (IgE), the latter of which contributes to the pathogenesis of atopic diseases. Although C epsilon CSR can occur directly from C mu, most mature peripheral B cells undergo CSR to C epsilon indirectly, namely from C mu to C gamma 1, and subsequently to C epsilon. Physiological mechanisms that influence CSR to C gamma 1 versus C. 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 C mu to C epsilon. Our findings suggest that IgE dysregulation in certain immunodeficiencies may be related to impaired B cell maturation.