Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B.
Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B.
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DOI：
10.4049/jimmunol.153.10.4357
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发表时间：
1994-11
影响因子：
4.4
通讯作者：
I. Berberich;G. Shu;E. Clark
中科院分区：
文献类型：
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作者：
I. Berberich;G. Shu;E. Clark
B 细胞相关表面分子 CD40 的作用是调节 B 细胞反应。 B 细胞上的 CD40 交联可导致同型细胞粘附、IL-6 产生，并与细胞因子结合导致 Ig 同型转换。酪氨酸激酶活性在与该受体结合后不久就会增加。关于 CD40 交联诱导的极早期事件如何与细胞反应联系起来，人们知之甚少。在这项研究中，我们证明，在静止的人扁桃体 B 细胞和 B 细胞系上交联 CD40 后，核因子 (NF)-kappa B 和 NF-kappa B 样转录因子被激活。激活是快速的，并通过酪氨酸激酶依赖性途径介导。电泳迁移率变动测定中检测到的复合物包含 p50、p65 (RelA)、c-Rel 和最可能的其他成分。通过使用瞬时转染测定，我们发现交联 CD40 支持 NF-κ B 依赖性基因表达。我们的结果将 NF-kappa B 系统定义为 CD40 信号传导的中间事件，并表明 CD40 途径可以影响具有 NF-kappa B 共有位点的 B 细胞相关基因的表达。
The B cell-associated surface molecule CD40 functions to regulate B cell responses. Cross-linking CD40 on B cells can lead to homotypic cell adhesion, IL-6 production, and, in combination with cytokines, to Ig isotype switching. Tyrosine kinase activity is increased shortly after engagement of this receptor. Little is known about how the very early events induced by CD40 cross-linking link to cellular responses. In this study, we demonstrate that nuclear factor (NF)-kappa B and NF-kappa B-like transcription factors are activated after cross-linking CD40 on resting human tonsillar B cells and on B cell lines. The activation is rapid and is mediated through a tyrosine kinase-dependent pathway. The complexes detected in electrophoretic mobility shift assays contain p50, p65 (RelA), c-Rel, and most likely other components. By using transient transfection assays, we found that cross-linking CD40 supports NF-kappa B-dependent gene expression. Our results define the NF-kappa B system as an intermediate event in CD40 signaling and suggest that the CD40 pathway can influence the expression of B cell-associated genes with NF-kappa B consensus sites.