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T细胞的直接相互作用和细胞因子的调节。在介绍研究中，我们在脐带和外周血B细胞中功能分析了CD27。将成年的外周血B细胞分离成CD27+和CD27-细胞，这些细胞在形态学中是不同的。脐带血B细胞未表达CD27，并且对外周血B细胞的CD27表达并联随着年龄的增长。只有CD27+ B细胞具有产生免疫球蛋白的能力，通过与与TNF相关的跨膜配体CD70接触而增加。成人外周血CD27+ B细胞可以进一步细分为两个离散亚型：IGD-CD27+和IGD+ CD27+ B细胞。 IgD-CD27+B细胞产生了IgG，IgM和IgA，其中IgD+CD27+B细胞主要产生IgM。添加了具有CD70活化的CD4+CD45ROT细胞CD70导致CD27在激活的B细胞上的CD27表达下降，并在激活的B细胞上添加了CD70的降低，并完全阻止了抗CD7的CD70 thy-by-cD70 MAB，指示了cD的COD70 MAB，指示了CD70 MAB，指示了CD70 MAB，指示了CD70 MAB，cD70 MAB，指示。在SAC和IL-2刺激下增加了免疫球蛋白的产生。通过CD27配体（CD70）在纯化的外周血B细胞上通过CD27触发CD27触发，在interleukin-100（IL-10）的存在下，血浆细胞数量增加（IL-10）。 CD27+B细胞中的IL-10和CD70转移剂的组合分化为浆细胞，但在CD27-B细胞中不存在。此外，将IL-2添加到IL-10和CD70转化激活系统中大大诱导了分化为浆细胞。在仅存在IL-2，IL-4或IL-6的情况下，CD70转移剂并未促进分化为浆细胞。另一方面，CD40信号通过主要由IL-2，IL-10和抗CD40 MAB激活的外周血B细胞增加了B细胞池的扩展。最后，CD27信号传导还反应了IL-10介导的凋亡中的B细胞。综上所述，我们的发现表明，通过CD27和IGD表达将外周血B细胞分离为亚群，并且CD27+B细胞通过与CD70分子的相互作用而产生大量的免疫球蛋白。这些数据还表明，CD27配体（CD70）是防止IL-10介导的凋亡促进并指导CD27+记忆B细胞与IL-10合作的血浆细胞的关键分子。较少的