首页> 外文期刊>Nature >Regulation of B-cell survival by BAFF-dependent PKC delta-mediated nuclear signalling
【24h】

Regulation of B-cell survival by BAFF-dependent PKC delta-mediated nuclear signalling

机译:依赖BAFF的PKCδ介导的核信号传导调节B细胞存活

获取原文
获取原文并翻译 | 示例
           

摘要

Approximately 65% of B cells generated in human bone marrow are potentially harmful autoreactive B cells(1). Most of these cells are clonally deleted in the bone marrow, while those autoreactive B cells that escape to the periphery are anergized or perish before becoming mature B cells(2-5). Escape of self-reactive B cells from tolerance permits production of pathogenic auto-antibodies(6); recent studies suggest that extended B lymphocyte survival is a cause of autoimmune disease in mice and humans(7). Here we report a mechanism for the regulation of peripheral B-cell survival by serine/threonine protein kinase Cdelta (PKCdelta): spontaneous death of resting B cells is regulated by nuclear localization of PKCdelta that contributes to phosphorylation of histone H2B at serine 14 (S14-H2B). We show that treatment of B cells with the potent B-cell survival factor BAFF ('B-cell-activating factor belonging to the TNF family') prevents nuclear accumulation of PKCdelta. Our data suggest the existence of a previously unknown BAFF-induced and PKCdelta-mediated nuclear signalling pathway which regulates B-cell survival.
机译:在人类骨髓中产生的B细胞中约有65%是潜在有害的自身反应性B细胞(1)。这些细胞大多数在骨髓中被克隆性缺失,而那些逃逸到周围的自反应性B细胞在变成成熟的B​​细胞之前被充氧或腐烂(2-5)。逃脱自我反应性B细胞的耐受性可产生致病性自身抗体(6);最近的研究表明,延长的B淋巴细胞存活是小鼠和人类自身免疫疾病的原因(7)。在这里我们报告了一种通过丝氨酸/苏氨酸蛋白激酶Cdelta(PKCdelta)调节外周B细胞存活的机制:静止B细胞的自发死亡受PKCdelta核定位的调节,这有助于在丝氨酸14(S14)上组蛋白H2B的磷酸化(S14 -H2B)。我们显示,用有效的B细胞存活因子BAFF(“属于TNF家族的B细胞活化因子”)治疗B细胞可防止PKCdelta的核积累。我们的数据表明存在以前未知的BAFF诱导和PKCdelta介导的调节B细胞存活的核信号通路。

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