INHIBITION OF HUMAN B-LYMPHOCYTE CELL-CYCLE PROGRESSION AND DIFFERENTIATION BY RAPAMYCIN
INHIBITION OF HUMAN B-LYMPHOCYTE CELL-CYCLE PROGRESSION AND DIFFERENTIATION BY RAPAMYCIN
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DOI：
10.1006/cimm.1994.1193
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发表时间：
1994-07-01
影响因子：
4.3
通讯作者：
JELINEK, DF
中科院分区：
文献类型：
--
作者：
AAGAARDTILLERY, KM;JELINEK, DF
在这项研究中，我们分析了免疫抑制剂雷帕霉素对高度纯化的正常人B淋巴细胞活化的影响。当使用多克隆活化剂金黄色葡萄球菌（SA）和可溶性CD 40配体（CD 40 L）刺激B细胞时，雷帕霉素抑制白细胞介素2（IL 2）依赖性和非依赖性增殖，以及IL 2依赖性分化为抗体分泌细胞。细胞周期分析表明，雷帕霉素抑制SA+ IL 2刺激的B细胞的进程通过细胞周期的中期-G（1）期。为了开始鉴定对B细胞活化至关重要的雷帕霉素敏感的信号传导事件，我们检测了雷帕霉素对p34（cdc 2）和p33（cdk 2）激酶活性的影响。SA+ IL 2刺激诱导两种细胞周期蛋白依赖性激酶的激活。有趣的是，雷帕霉素消除了p34（cdc 2）和p33（cdk 2）的激活。因此，我们的研究结果表明，雷帕霉素抑制了一些SA-和CD 40 L-诱导的事件，可能是必要的进入S期，并允许随后的B细胞分化。这些研究强调了这种药物作为一种工具的效用，开始解剖人B鳗鱼利用的激活途径，以及提供雷帕霉素在体内的治疗用途的影响。(C)1994年出版社出版。
In this study, we have analyzed the effects of the immunosuppressive agent rapamycin on the activation of highly purified normal human B lymphocytes. When the polyclonal activators Staphylococcus aureus (SA) and soluble CD40 ligand (CD40L) were used to stimulate B cells, rapamycin inhibited both interleukin 2 (IL2)-dependent and -independent proliferation, as well as IL2-dependent differentiation into antibody-secreting cells. Cell cycle analysis indicated that rapamycin inhibited the progression of SA+IL2-stimulated B cells past the mid-G(1) phase of the cell cycle. To begin to identify rapamycin-sensitive signaling events essential for B cell activation, we examined the effects of rapamycin on p34(cdc2) and p33(cdk2) kinase activities. SA+IL2 stimulation induced the activation of both cyclin-dependent kinases. Of interest, rapamycin abrogated the activation of both p34(cdc2) and p33(cdk2). Our results indicate therefore that rapamycin inhibits a number of SA- and CD40L-inducible events that may be necessary for both entry into S phase and for permitting subsequent B cell differentiation. These studies emphasize the utility of this drug as a tool to begin to dissect the activation pathways utilized by human B eels, as well as to provide implications for the therapeutic use of rapamycin in vivo. (C) 1994 Academic Press, Inc.