标题：Homodimerization of the human interleukin 4 receptor α chain induces Cɛ germline transcripts in B cells in the absence of the interleukin 2 receptor γ chain
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：1997
卷号：94
期号：11
页码：5866-5871
DOI：10.1073/pnas.94.11.5866
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The cytokines interleukin (IL)-4 and IL-13 play a critical role in inducing C{varepsilon} germline transcripts and IgE isotype switching in human B cells. The IL-4 receptor (IL-4R) in B cells is composed of two chains, the IL-4-binding IL-4R chain, which is shared with the IL-13R, and the IL-2R{gamma} ({gamma}c) chain, which is shared with IL-7R, IL-9R, and IL-15R. IL-4 induces C{varepsilon} germline transcripts and IgE isotype switching in B cells from patients with {gamma}c chain deficiency. Induction of C{varepsilon} germline transcripts by IL-4 in B cells that lack the {gamma}c chain may involve signaling via the IL-13R. Alternatively, the IL-4R chain may transduce intracellular signals that lead to C{varepsilon} gene transcription independently of its association with other chains. We show that ligand-induced homodimerization of chimeric surface receptors consisting of the extracellular and transmembrane domains of the erythropoietin receptor and of the intracellular domain of IL-4R induces Janus kinase 1 (Jak1) activation, STAT6 activation, and C{varepsilon} germline transcripts in human B cell line BJAB. Disruption of the Jak1-binding proline-rich Box1 region of IL-4R abolished signaling by this chimeric receptor. Furthermore, B cells transfected with a chimeric CD8/IL-4R receptor, which is expressed on the cell surface as a homodimer, constitutively expressed C{varepsilon} germline transcripts. These results suggest that homodimerization of the IL-4R chain is sufficient to transduce Jak1-dependent intracellular signals that lead to IgE isotype switching.
