CD27/CD70 interactions in B cell immunoglobulin production

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。在目前的研究中，Wer对脐带血和外周血B细胞中的CD27进行了功能分析。成人外周血B细胞分为CD27+和CD27-两种形态不同的细胞。脐血B细胞不表达CD27，外周血B细胞CD27表达随年龄增加而增加。只有CD27+B细胞有能力产生免疫球蛋白，这种免疫球蛋白通过与肿瘤坏死因子相关的跨膜配体CD70接触而增加。成人外周血CD27+B细胞可进一步分为两个亚型：IGD-CD27+和IGD+CD27+B细胞。活化的CD_4~+CD_(45)T细胞可下调活化B细胞表面CD_(27)的表达，其下调作用可被抗CD_(70)单抗完全阻断，提示T-B细胞直接参与…通过CD27/CD70更得体。在SAC+IL-2刺激下，CD27和CD40的激活增加了免疫球蛋白的产生，CD27配体(CD70)激活纯化的外周血B细胞，在有IL-10存在的情况下，血浆细胞的数量增加。联合应用IL-10和CD70基因可诱导CD27+B细胞分化为浆细胞，而CD27-B细胞不分化为浆细胞。此外，在IL-10和CD70-转基因激活系统中加入IL-2可显著诱导其向浆细胞分化。在单独存在IL-2、IL-4或IL-6的情况下，CD70-转基因细胞不能促进其向浆细胞分化。另一方面，CD40信号增加了外周血中主要由IL-2、IL-10和抗CD40单抗激活的B细胞池的扩张。最后，CD27信号也将B细胞从IL-10介导的凋亡中解救出来。综上所述，我们的研究结果表明，外周血B细胞通过CD27和IGD的表达被分成不同的亚群，CD27+B细胞通过与CD70分子的相互作用产生大量的免疫球蛋白。CD27配体(CD70)是阻止IL-10介导的促凋亡和与IL-10协同引导CD27+记忆B细胞向浆细胞分化的关键分子。较少

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