Yoshino T, Kondo E, Cao L, Takahashi K, Hayashi K, Nomura S, Akagi T
Department of Pathology, Okayama University School of Medicine, Japan.
Blood. 1994 Apr 1;83(7):1856-61.
To examine the regulatory mechanism of apoptosis in lymphoid cells, expression of both bcl-2 protein and Fas antigen was investigated in reactive lymph nodes, in resting lymphocytes from peripheral blood (PBLs), and in PBLs stimulated with pokeweed mitogen, interleukin-4 (IL-4) + anti-IgM antibody, IL-2 + anti-CD3 antibody, phytohemagglutinin + phorbol myristate acetate using immunohistochemistry and flow cytometry. Germinal center cells expressed a large amount of Fas antigen, which is associated with the induction of apoptosis in lymphoid cell lines, in contrast to the lack of bcl-2 protein as an apoptosis inhibitor. On the other hand, mantle zone lymphocytes expressed a high level of bcl-2 protein and less Fas antigen. This inverse expression of bcl-2 protein and Fas antigen was also shown in activated T and B lymphocytes from peripheral blood. These lymphoblasts fell into apoptosis dose-dependently in the presence of anti-Fas monoclonal antibody, but resting lymphocytes that expressed both bcl-2 protein and Fas antigen did not undergo apoptosis. These findings suggest that bcl-2 expression prevents the apoptosis of lymphoid cells induced by the Fas antigen-dependent mechanism and that apoptosis of lymphocytes is exquisitely controlled, at least in part, by regulation of the bcl-2 and Fas genes.
为研究淋巴细胞凋亡的调控机制，采用免疫组织化学和流式细胞术，对反应性淋巴结、外周血静息淋巴细胞（PBLs）以及用商陆丝裂原、白细胞介素-4（IL-4）+抗IgM抗体、IL-2+抗CD3抗体、植物血凝素+佛波酯刺激后的PBLs中的bcl-2蛋白和Fas抗原表达进行了研究。生发中心细胞表达大量Fas抗原，Fas抗原与淋巴细胞系凋亡的诱导相关，而作为凋亡抑制因子的bcl-2蛋白缺乏。另一方面，套区淋巴细胞表达高水平的bcl-2蛋白且Fas抗原较少。外周血活化的T和B淋巴细胞中也显示出bcl-2蛋白和Fas抗原的这种相反表达。在抗Fas单克隆抗体存在的情况下，这些淋巴母细胞呈剂量依赖性凋亡，但同时表达bcl-2蛋白和Fas抗原的静息淋巴细胞未发生凋亡。这些发现表明，bcl-2表达可防止由Fas抗原依赖性机制诱导的淋巴细胞凋亡，并且淋巴细胞的凋亡至少部分地通过bcl-2和Fas基因的调控受到精确控制。
