期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：2
页码：821-826
DOI：10.1073/pnas.0909235107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：IL-4 signaling promotes IgE class switching through STAT6 activation and the induction of Ig germ-line {varepsilon} (GL{varepsilon}) 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{varepsilon} 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{varepsilon} transcripts. Moreover, NFIL3 binds to I{varepsilon} promoter in vivo. Together, these results identify NFIL3 as a key regulator of IL-4-induced GL{varepsilon} transcription in response to IL-4 and subsequent IgE class switching.
关键词：IL-4 signal ; immunoglobulin ; germ-line transcription
