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人扁桃体B细胞和伯基特淋巴瘤细胞的激活及激活诱导的死亡:CD95(Fas/APO-1)配体表达及功能的缺失

Activation and activation-induced death of human tonsillar B cells and Burkitt lymphoma cells: lack of CD95 (Fas/APO-1) ligand expression and function.

作者信息

Daniel P T, Oettinger U, Mapara M Y, Bommert K, Bargou R, Dörken B

机构信息

Max Delbrück Center for Molecular Medicine, Berlin, Germany.

出版信息

Eur J Immunol. 1997 Apr;27(4):1029-34. doi: 10.1002/eji.1830270433.

Abstract

Activation of T cells was shown to up-regulate the Fas ligand (FasL) which binds to the CD95 (APO-1/Fas) antigen and mediates activation-induced cell death (AICD) of activated T cells and T lymphoma cells. A recent report showed that mouse B cells express the FasL upon activation with lipopolysaccharide (LPS). We therefore asked whether activation of human B cells induces expression of FasL and whether AICD is mediated, as in T cells, through autocrine production of the FasL. We used human tonsillar B cells and Burkitt lymphoma cell lines which were activated by CD40 ligand, surface (s)IgM cross-linking, or LPS. Northern and Western blot analysis failed to detect FasL during B cell activation or AICD of both normal and malignant B cells. Low-level expression of FasL was detected by reverse transcriptase-polymerase chain reaction. Functional experiments, however, showed that FasL is not functionally expressed upon activation. IgM-mediated AICD in the tonsillar or Burkitt lymphoma B cells could not be inhibited by FasL blocking. Thus, our data show that, in contrast to T cells, activation of normal or malignant human B cells does not lead to functional FasL expression.

摘要

已表明T细胞的激活会上调Fas配体(FasL),该配体与CD95(APO-1/Fas)抗原结合,并介导活化的T细胞和T淋巴瘤细胞的活化诱导细胞死亡(AICD)。最近的一份报告显示,小鼠B细胞在用脂多糖(LPS)激活后会表达FasL。因此,我们询问人类B细胞的激活是否会诱导FasL的表达,以及AICD是否像在T细胞中一样通过FasL的自分泌产生来介导。我们使用了人类扁桃体B细胞和伯基特淋巴瘤细胞系,它们通过CD40配体、表面(s)IgM交联或LPS激活。Northern和Western印迹分析未能在正常和恶性B细胞的B细胞激活或AICD过程中检测到FasL。通过逆转录聚合酶链反应检测到FasL的低水平表达。然而,功能实验表明,激活后FasL没有功能性表达。FasL阻断不能抑制扁桃体或伯基特淋巴瘤B细胞中IgM介导的AICD。因此,我们的数据表明,与T细胞不同,正常或恶性人类B细胞的激活不会导致功能性FasL表达。

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