Schattner Elaine J, Friedman Steven M, Casali Paolo
Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Autoimmunity. 2002 Jul;35(4):283-9. doi: 10.1080/0891693021000002072.
Apoptotic deletion of expanded B cell populations is essential in avoidance of autoimmune disease and immune regulation of some B cell malignancies. The role of CD4+ T cells in B cell apoptosis is evident from the high incidence of B cell tumors and autoimmunity in patients with T cell diseases such as the acquired immune deficiency syndrome (AIDS). We have previously demonstrated that in Epstein-Barr Virus (EBV) negative Burkitt's lymphoma (BL), a tumor derived from proliferating centroblasts of the germinal center, the malignant lymphocytes can be induced to express Fas (CD95) by ligation of CD40 at the B cell surface. Upon CD40 engagement, BL cells are sensitized to T-cell derived death signals provided by Fas ligand (FasL, CD95L). HBL-3 is a cell line derived from an AIDS-related BL in which the tumor IgM binds the human erythrocyte "i" antigen. To determine whether Fas-mediated apoptosis of BL cells is reduced in the context of antigen to which the tumor IgM binds, we stimulated HBL-3 cells with CD40 ligand (CD40L, CD154) in the presence and absence of human erythrocytes expressing the "i" antigen, and measured Fas-mediated apoptosis upon exposure to an agonistic anti-Fas antibody. We observed that HBL-3 cells were sensitized to Fas-mediated death by exposure to CD40L. When i+ RBCs were present, Fas-mediated apoptosis in HBL-3 cells was reduced by greater than 30%. In contrast, there was no reduction in Fas-mediated apoptosis in the presence of i- (I+) RBCs. These findings demonstrate that Fas-mediated deletion of BL cells is inhibited upon surface IgM engagement by antigen for which the malignant clone has affinity.
扩增的B细胞群体的凋亡性清除对于避免自身免疫性疾病和某些B细胞恶性肿瘤的免疫调节至关重要。CD4 + T细胞在B细胞凋亡中的作用从患有T细胞疾病（如获得性免疫缺陷综合征（AIDS））的患者中B细胞肿瘤和自身免疫的高发病率中可见一斑。我们之前已经证明，在爱泼斯坦 - 巴尔病毒（EBV）阴性的伯基特淋巴瘤（BL）中，一种源自生发中心增殖中心母细胞的肿瘤，通过在B细胞表面连接CD40可诱导恶性淋巴细胞表达Fas（CD95）。在CD40参与后，BL细胞对由Fas配体（FasL，CD95L）提供的T细胞衍生的死亡信号敏感。HBL - 3是一种源自与AIDS相关的BL的细胞系，其中肿瘤IgM结合人红细胞“i”抗原。为了确定在肿瘤IgM结合的抗原背景下BL细胞的Fas介导的凋亡是否减少，我们在存在和不存在表达“i”抗原的人红细胞的情况下，用CD40配体（CD40L，CD154）刺激HBL - 3细胞，并在暴露于激动性抗Fas抗体后测量Fas介导的凋亡。我们观察到，通过暴露于CD40L，HBL - 3细胞对Fas介导的死亡敏感。当存在i +红细胞时，HBL - 3细胞中Fas介导的凋亡减少超过30％。相比之下，在存在i - （I +）红细胞的情况下，Fas介导的凋亡没有减少。这些发现表明，当恶性克隆具有亲和力的抗原与表面IgM结合时，Fas介导的BL细胞清除受到抑制。
