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首页> 外文期刊>Molecular and Cellular Biology >Activation of NF-kappaB/Rel by CD40 engagement induces the mouse germ line immunoglobulin Cgamma1 promoter.
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Activation of NF-kappaB/Rel by CD40 engagement induces the mouse germ line immunoglobulin Cgamma1 promoter.

机译：CD40参与激活NF-κB/ Rel可诱导小鼠种系免疫球蛋白Cgamma1启动子。

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Interaction between CD40 on B cells and CD40 ligand (CD40L) on T cells has been shown to mediate T-cell contact help for B-cell proliferation, differentiation, and immunoglobulin isotype switching. It has recently been shown that cross-linking CD40 on mouse B cells induces germ line gamma1 and epsilon transcripts and that interleukin-4 synergizes with CD40 signaling to further induce these germ line transcripts. Germ line transcripts have been shown to be required for class switch recombination. Here we show that signaling via CD40 increases expression of a transiently transfected luciferase reporter plasmid driven by the germ line Cgamma1 promoter in M12.4.1 B-lymphoma cells. By linker-scanning mutation analysis of the promoter, we have identified a CD40-responsive region (CD40RR) which is able to confer inducibility by CD40L to a minimal c-fos promoter. The CD40RR contains three binding sites for NF-kappaB/Rel proteins which are each required for maximal induction of CD40RR activity by CD40L. Binding of the NF-kappaB/Rel proteins p50, p65, c-Rel, and RelB to the CD40RR is induced by CD40 signaling in M12.4.1 cells and in splenic B cells. Cotransfection of expression plasmids for p50 and p65 or p50 and RelB, but not c-Rel, into M12.4.1 cells transactivates the CD40RR and the germ line gamma1 promoter. These data demonstrate that NF-kappaB Rel proteins activated by CD40 ligation play an important role in induction of the germ line Cgamma1 promoter.
机译：B细胞上的CD40与T细胞上的CD40配体（CD40L）之间的相互作用已显示出介导的T细胞接触帮助B细胞增殖，分化和免疫球蛋白同种型转换。最近显示，在小鼠B细胞上交联的CD40诱导种系gamma1和epsilon转录物，白介素4与CD40信号传导协同作用进一步诱导这些种系转录物。业已证明，种系重组需要胚系转录本。在这里，我们显示了通过CD40发出的信号增加了M12.4.1 B淋巴瘤细胞中由种系Cgamma1启动子驱动的瞬时转染的荧光素酶报道基因质粒的表达。通过启动子的接头扫描突变分析，我们确定了一个CD40反应区（CD40RR），该区能够将CD40L诱导为最小的c-fos启动子。 CD40RR包含NF-κB/ Rel蛋白的三个结合位点，每个结合位点都是CD40L最大限度地诱导CD40RR活性所必需的。 NF-κB/ Rel蛋白p50，p65，c-Rel和RelB与CD40RR的结合在M12.4.1细胞和脾B细胞中通过CD40信号传导来诱导。将p50和p65或p50和RelB的表达质粒（而非c-Rel）共转染到M12.4.1细胞中，可将CD40RR和种系gamma1启动子反式激活。这些数据表明，通过CD40连接激活的NF-κBRel蛋白在诱导生殖系Cgamma1启动子中起重要作用。

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