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CD27/CD70 interactions in B cell immunoglobulin production

B 细胞免疫球蛋白生产中的 CD27/CD70 相互作用

基本信息

批准号：
07670854
负责人：
AGEMATSU Kazunaga
金额：
$ 1.22万
依托单位：
Dept.of Pediatr., Shinshu Univ.Sch.of Med.
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670854/
关键词：
Plasma cells Memory B cells CD27 CD70 Naive B cells 免疫応答 B細胞ヘルパーT細胞 Immunoglolulin

项目摘要

B cell immunoglobulin production is regulated by direct interaction and cytokines of helper T cells. In the present studies, wer had functionally analyzed CD27 in cord and peripheral blood B cells. Adult peripheral blood B cells were separated into CD27+ and CD27- cells, which were different in the morphology. Cord blood B cells did not express CD27, and CD27 expression on peripheral blood B cells increased with age in parallel. Only CD27+ B cells had ability to produce immunoglobulin, which was increased by contact with a TNF-related transmembrane ligand, CD70. Adult peripheral blood CD27+ B cells can be further subdivided into two discrete subtypes : IgD-CD27+ and IgD+CD27+B cells. IgD-CD27+B cells produced IgG,IgM and IgA,where as IgD+CD27+B cells predominantly produce IgM.The addition of activated CD4+CD45ROT cells with CD70 caused down-regulation of CD27 expression on activated B cells, and its down modulation was completely blocked by anti-CD70 mAb, indicating direct T-B cell con … More tact via CD27/CD70. The triggering via CD27 and CD40 additively increased the immunoglobulin production under SAC plus IL-2 stimulation.The triggering via CD27 by CD27 ligand (CD70) on purified peripheral blood B cells yielded an increase in the number of plasma cells in the presence of interleukin-10 (IL-10). The differentiation into plasma cells by a combination of IL-10 and CD70-transfectants occurred in CD27+B cells, but not in CD27-B cells. Moreover, the addition of IL-2 to the IL-10 and CD70-transfect activation system greatly induced the differentiation into plasma cells. In the presence of only IL-2, IL-4 or IL-6, CD70-transfectants did not promote the differentiation into plasma cells. On the other hand, CD40 signaling increased the expansion of a B cell pool from peripheral blood B cells primarily activated by IL-2, IL-10 and anti-CD40 mAb. Finally, CD27 signaling also rescued B cells from IL-10-mediated apoptosis. Taken together, our findings demonstrate peripheral blood B cells are separated into subpopulations by CD27 and IgD expression and that CD27+B cells produce large amounts of immunoglobulin by the interaction with CD70 molecule. These data also demonstrate that CD27 ligand (CD70) is a key molecule to prevent the IL-10-mediated promotion of apoptosis and to direct the differentiation of CD27+memory B cells toward plasma cells in cooperation with IL-10. Less

B细胞免疫球蛋白的产生受辅助性T细胞的直接相互作用和细胞因子的调节。本研究对脐血和外周血B细胞中的CD 27进行了功能分析。成人外周血B细胞分为CD 27+和CD 27-两种细胞，两种细胞形态不同。脐血B细胞不表达CD 27，外周血B细胞上CD 27的表达随年龄平行增加。只有CD 27 + B细胞具有产生免疫球蛋白的能力，其通过与TNF相关的跨膜配体CD 70接触而增加。成人外周血CD 27 + B细胞可进一步细分为两个离散的亚型：IgD-CD 27+和IgD+ CD 27 +B细胞。IgD-CD 27 +B细胞主要产生IgG、IgM和伊加，而IgD+ CD 27 +B细胞主要产生IgM。活化的CD 4 + CD 45 ROT细胞与CD 70共同作用可使活化的B细胞表面CD 27表达下调，其下调作用可被抗CD 70单抗完全阻断，表明T-B细胞直接与CD 45 ROT细胞共同作用。 ...更多信息通过CD 27/CD 70进行接触。在SAC + IL-2刺激下，通过CD 27和CD 40的触发可相加地增加免疫球蛋白的产生，而在IL-10（IL-10）存在下，通过CD 27被CD 27配体（CD 70）对纯化的外周血B细胞的触发可增加浆细胞的数量。IL-10和CD 70-转染子的组合在CD 27 +B细胞中发生向浆细胞的分化，但在CD 27-B细胞中不发生。此外，在IL-10和CD 70-介导的活化系统中加入IL-2可显著诱导细胞向浆细胞分化。在仅存在IL-2、IL-4或IL-6的情况下，CD 70转染子不促进向浆细胞的分化。另一方面，CD 40信号传导增加了来自主要由IL-2、IL-10和抗CD 40 mAb激活的外周血B细胞的B细胞池的扩增。最后，CD 27信号还从IL-10介导的凋亡中拯救了B细胞。综上所述，我们的研究结果表明，外周血B细胞通过CD 27和IgD表达分成亚群，并且CD 27 +B细胞通过与CD 70分子的相互作用产生大量的免疫球蛋白。这些数据还表明，CD 27配体（CD 70）是阻止IL-10介导的细胞凋亡促进和与IL-10合作指导CD 27+记忆B细胞向浆细胞分化的关键分子。少