首页> 外文期刊>Nature >SAP-controlled T-B cell interactions underlie germinal centre formation
【24h】

SAP-controlled T-B cell interactions underlie germinal centre formation

机译:SAP控制的T-B细胞相互作用是生发中心形成的基础

获取原文
获取原文并翻译 | 示例
           

摘要

Generation of long-term antibody-mediated immunity depends on the germinal centre reaction, which requires cooperation between antigen-specific T and B lymphocytes. In human X-linked lymphoproliferative disease and its gene-targeted mouse model, loss-of-function mutations in signalling lymphocyte activation molecule-associated protein (SAP, encoded by SH2D1a) cause a profound defect in germinal centre formation by an as yet unknown mechanism. Here, using two-photon intravital imaging, we show that SAP deficiency selectively impairs the ability of CD4~+ T cells to stably interact with cognate B cells but not antigen-presenting dendritic cells. This selective defect results in a failure of antigen-specific B cells to receive adequate levels of contact-dependent T-cell help to expand normally, despite Sap~(-/-) T cells exhibiting the known characteristics of otherwise competent helper T cells. Furthermore, the lack of stable interactions with B cells renders Sap~(-/-) T cells unable to be efficiently recruited to and retained in a nascent germinal centre to sustain the germinal centre reaction. These results offer an explanation for the germinal centre defect due to SAP deficiency and provide new insights into the bi-directional communication between cognate T and B cells in vivo.
机译:长期抗体介导的免疫的产生取决于生发中心反应,这需要抗原特异性T和B淋巴细胞之间的配合。在人类X连锁的淋巴增生性疾病及其以基因为靶点的小鼠模型中,信号转导淋巴细胞活化分子相关蛋白(SAP,由SH2D1a编码)中的功能丧失突变通过尚不清楚的机制引起生发中心形成的严重缺陷。 。在这里,使用双光子活体成像,我们表明SAP缺乏选择性地损害CD4〜+ T细胞与同源B细胞稳定相互作用而不是抗原呈递树突状细胞稳定相互作用的能力。这种选择性缺陷导致抗原特异性B细胞无法接受足够水平的接触依赖性T细胞帮助,从而无法正常扩展,尽管Sap _(-/-)T细胞表现出其他胜任的辅助T细胞的已知特征。此外,缺乏与B细胞的稳定相互作用使得Sap-(-/-)T细胞不能有效地募集并保留在新生的生发中心中以维持生发中心反应。这些结果为由于SAP缺乏引起的生发中心缺陷提供了解释,并为体内同源T细胞和B细胞之间的双向通讯提供了新见解。

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