McFadden H J, Koshland M E
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11027-31. doi: 10.1073/pnas.88.24.11027.
In a primary immune response, B cells require signals from the T-cell lymphokines interleukins 2 and 5 (IL-2 and IL-5) to develop into IgM-secreting cells. One role of IL-2 and IL-5 is to activate transcription of the gene encoding the IgM joining component, the J chain. In this study the activation mechanism was investigated by using an inducible beta-lymphoma cell line to examine J-chain RNA expression and factor binding to the J-chain promoter. The analyses revealed that both IL-2 and IL-5 trigger a decrease in the binding of two promoter-specific nuclear proteins that precedes the appearance of J-chain RNA. In combination the two lymphokines effected nearly additive changes in factor binding and J-chain RNA abundance. Both effects were reversed upon withdrawal of the lymphokine stimulus and both were inhibited in the presence of the T-cell lymphokine IL-4. These findings indicate that the IL-2 and IL-5 signal pathways converge to deliver a common signal that regulates the repressor activities of two lymphokine-responsive promoter elements.
在初次免疫应答中,B细胞需要来自T细胞淋巴因子白细胞介素2和5(IL-2和IL-5)的信号才能发育成分泌IgM的细胞。IL-2和IL-5的一个作用是激活编码IgM连接成分J链的基因的转录。在本研究中,通过使用一种可诱导的β淋巴瘤细胞系来检测J链RNA表达以及因子与J链启动子的结合,对激活机制进行了研究。分析显示,在J链RNA出现之前,IL-2和IL-5都会引发两种启动子特异性核蛋白结合的减少。两种淋巴因子共同作用时,在因子结合和J链RNA丰度方面产生了几乎相加的变化。在撤除淋巴因子刺激后,这两种效应都被逆转,并且在T细胞淋巴因子IL-4存在的情况下,这两种效应都受到抑制。这些发现表明,IL-2和IL-5信号通路汇聚以传递一个共同信号,该信号调节两种淋巴因子反应性启动子元件的阻遏物活性。