...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Unique CD40-mediated biological program in B cell activation requires both type 1 and type 2 NF-kappaB activation pathways.
【24h】

Unique CD40-mediated biological program in B cell activation requires both type 1 and type 2 NF-kappaB activation pathways.

机译：B细胞活化中独特的CD40介导的生物学程序需要1型和2型NF-κB活化途径。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

B lymphocytes can be activated by many different stimuli. However, the mechanisms responsible for the signaling and functional specificities of individual stimuli remain to be elucidated. Here, we have compared the contribution of the type 1 (p50-dependent) and type 2 (p52-dependent) NF-kappaB activation pathways to cell survival, proliferation, homotypic aggregation, and specific gene regulation of murine primary B lymphocytes. Whereas lipopolysaccharide (LPS) and B cell activation factor (BAFF) mainly activate the type 1 or type 2 pathways, respectively, CD40 ligand (CD40L) strongly activates both. Rescue of spontaneous apoptosis is diminished in p52(-/-) B cells after BAFF stimulation and in p50(-/-)c-Rel(-/-) B cells after LPS stimulation. Interestingly, significant CD40-induced B cell survival is still observed even in p50(-/-)c-Rel(-/-)p65(-/+) B cells, which is correlated with the ability of CD40L to up-regulate Bcl-x(L) expression in these cells. CD40L- and LPS-induced B cell proliferation, as well as up-regulation of proliferation-related genes, however, are greatly reduced in c-Rel(-/-) and p50(-/-)c-Rel(-/-) B cells but are normal in p52(-/-) B cells. We have further demonstrated that both c-Rel and p52 are required for CD40-mediated B cell homotypic aggregation, which explains well why neither LPS nor BAFF has this function. Overall, our studies suggest that both type 1 and type 2 NF-kappaB pathways contribute to the gene expression and biological program unique for CD40 in B cell activation.
机译：B淋巴细胞可以被许多不同的刺激激活。然而，负责个体刺激的信号传导和功能特异性的机制仍有待阐明。在这里，我们比较了1型（p50依赖性）和2型（p52依赖性）NF-kappaB激活途径对鼠原代B淋巴细胞的细胞存活，增殖，同型聚集和特定基因调控的贡献。脂多糖（LPS）和B细胞激活因子（BAFF）主要分别激活1型或2型途径，而CD40配体（CD40L）则强烈激活这两种途径。 BAFF刺激后p52（-/-）B细胞和LPS刺激后p50（-/-）c-Rel（-/-）B细胞中自发凋亡的减少。有趣的是，即使在p50（-/-）c-Rel（-/-）p65（-/ +）B细胞中，仍观察到了显着的CD40诱导的B细胞存活，这与CD40L上调Bcl的能力相关-x（L）在这些细胞中的表达。 CD40L和LPS诱导的B细胞增殖以及增殖相关基因的上调在c-Rel（-/-）和p50（-/-）c-Rel（-/- ）B细胞，但在p52（-/-）B细胞中正常。我们进一步证明了CD40介导的B细胞同型聚集需要c-Rel和p52，这很好地解释了为什么LPS和BAFF都不具有此功能。总体而言，我们的研究表明1型和2型NF-kappaB途径都有助于B细胞活化CD40的基因表达和生物学程序。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号