Yoshino T, Cao L, Nishiuchi R, Matsuo Y, Yamadori I, Kondo E, Teramoto N, Hayashi K, Takahashi K, Kamikawaji N
Department of Pathology, School of Medicine, Okayama University, Japan.
Eur J Immunol. 1995 Aug;25(8):2190-4. doi: 10.1002/eji.1830250811.
CD95 (Fas antigen/APO-1) is up-regulated in activated lymphocytes, and monoclonal antibody (mAb) to CD95 induces apoptosis. HLA class II molecules play a key role in antigen presentation, ligation of which induces signal transduction. We examined 18 lymphoid cell lines (15 B cell and 3 T cell lines) to investigate the effects of ligation of HLA class II molecules on CD95-mediated apoptosis. All of the five immature B cell lines were sensitive to anti-CD95 mAb, and ligation of HLA class II molecules promoted CD95-mediated apoptosis. In seven B-blastoid cell lines, two Burkitt lines were resistant to anti-CD95 mAb in spite of high expression of CD95. In three of five non-Burkitt B-blastoid lines, CD95-mediated apoptosis was augmented by treatment with anti-HLA class II mAb, while the other two lines lacking CD95 were resistant to anti-CD95 mAb. Three plasmacytic cell lines showed CD95-mediated apoptosis, but enhancement by anti-HLA class I mAb was slight in one cell line and was not observed in the other two lines. Out of three HLA class II antigen-positive T cell lines, CD95-mediated apoptosis was observed to some degree in one call line but was not promoted by the treatment with anti-HLA class II mAb, and the other two cell lines were resistant to anti-CD95 mAb. Ligation of HLA class II molecules did not alter CD95 expression in the five cell lines examined, except Su-DHL-4 originated from a follicular lymphoma, which showed slight up-regulation. Taken together, ligation of HLA class II molecules apparently promotes CD95-mediated apoptosis in immature B cells and non-Burkitt B blasts. These findings highlight the role of HLA class II molecules in CD95-mediated apoptosis, which may facilitate rapid clearance of functionally useless cells from the immune system and might be involved in negative selection of B cells.
CD95（Fas抗原/APO-1）在活化淋巴细胞中上调，抗CD95单克隆抗体（mAb）可诱导细胞凋亡。HLA II类分子在抗原呈递中起关键作用，其连接可诱导信号转导。我们检测了18种淋巴细胞系（15种B细胞系和3种T细胞系），以研究HLA II类分子连接对CD95介导的细胞凋亡的影响。所有5种未成熟B细胞系均对抗CD95 mAb敏感，HLA II类分子的连接促进了CD95介导的细胞凋亡。在7种B淋巴母细胞样细胞系中，尽管CD95高表达，但2种伯基特细胞系对抗CD95 mAb耐药。在5种非伯基特B淋巴母细胞样细胞系中的3种中，抗HLA II类mAb处理增强了CD95介导的细胞凋亡，而另外2种缺乏CD95的细胞系对抗CD95 mAb耐药。3种浆细胞系表现出CD95介导的细胞凋亡，但抗HLA I类mAb在1种细胞系中的增强作用轻微，在另外2种细胞系中未观察到增强作用。在3种HLA II类抗原阳性T细胞系中，1种细胞系有一定程度的CD95介导的细胞凋亡，但抗HLA II类mAb处理未促进其凋亡，另外2种细胞系对抗CD95 mAb耐药。除源于滤泡性淋巴瘤的Su-DHL-4有轻微上调外，HLA II类分子的连接在检测的5种细胞系中未改变CD95表达。综上所述，HLA II类分子的连接明显促进未成熟B细胞和非伯基特B母细胞中CD95介导的细胞凋亡。这些发现突出了HLA II类分子在CD95介导的细胞凋亡中的作用，这可能有助于从免疫系统中快速清除功能无用的细胞，并可能参与B细胞的阴性选择。
