期刊
CYTOKINE
卷 57, 期 3, 页码 360-371出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2011.12.001
关键词
Type I interferons; BCL-6; Burkitt's lymphoma
资金
- Swedish Cancer Society(Cancerfonden), Karolinska Institutet and Swedish Research Council
- Cancer Research Fellowship of the Cancer Research Institute (New York)/Concern Foundation (Los Angeles)
Type I interferons (IFN) exert multiple effects on both the innate and adaptive immune system in addition to their antiviral and antiproliferative activities. Little is known, however about the direct effects of type IFNs on germinal center (GC) B cells, the central components of adaptive B cell responses. We used Burkitt's lymphoma (BL) lines, as a model system of normal human GC B cells, to examine the effect of type I IFNs on the expression of BCL-6, the major regulator of the GC reaction. We show that type I IFNs, but not IFN gamma, IL-2 and TNF alpha rapidly down-regulate BCL-6 protein and mRNA expression, in cell lines derived from endemic, but not from sporadic BL. IFN alpha-induced down-regulation is specific for BCL-6, independent of Epstein-Barr virus and is not accompanied by IRF-4 up-regulation. IFN alpha-induced BCL-6 mRNA down-regulation does not require de novo protein synthesis and is specifically inhibited by piceatannol. The proteasome inhibitor mG132 non-specifically prevents, while inhibitors of alternate type I IFN signaling pathways do not inhibit IFNa-induced BCL-6 protein downregulation. We validate our results with showing that IFN alpha rapidly down-regulates BCL-6 mRNA in purified mouse normal GC B cells. Our results identify type I IFNs as the first group of cytokines that can down-regulate BCL-6 expression directly in GC B cells. (C) 2011 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据