IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching

IL-4 signaling promotes IgE class switching through STAT6 activation and the induction of Ig germ-line epsilon (GL epsilon) transcription. Previously, we and others identified a transcription factor, Nfil3, as a gene induced by IL-4 stimulation in B cells. However, the precise roles of nuclear factor, IL-3-regulated (NFIL3) in IL-4 signaling are unknown. Here, we report that NFIL3 is important for IgE class switching. NFIL3-deficient mice show impaired IgE class switching, and this defect is B-cell intrinsic. The induction of GL epsilon transcripts after LPS and IL-4 stimulation is significantly reduced in NFIL3-deficient B cells. Expression of NFIL3 in NFIL3-deficient B cells restores the impairment of IgE production, and overexpression of NFIL3 in the presence of cycloheximide induces GL epsilon transcripts. Moreover, NFIL3 binds to I epsilon promoter in vivo. Together, these results identify NFIL3 as a key regulator of IL-4-induced GL epsilon transcription in response to IL-4 and subsequent IgE class switching.