Ishigami T, Kim K M, Horiguchi Y, Higaki Y, Hata D, Heike T, Katamura K, Mayumi M, Mikawa H
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
J Immunol. 1992 Jan 15;148(2):360-8.
We investigated the mechanisms of anti-IgM antibody-induced cell death in a recently established human surface IgM+ IgD+ B lymphoma cell line, B104, the growth of which is irreversibly inhibited by anti-IgM antibody but not by anti-IgD antibody, and compared it with the cell death of T cells via TCR/CD3 complex and with the cell death of a murine anti-IgM antibody-sensitive B lymphoma cell line, WEHI-231. The rapid time course of B104 cell death and its requirements for de novo macromolecular synthesis and Ca2+ influx suggest that anti-IgM antibody-induced B104 cell death is an active Ca(2+)-dependent programmed cell death. Moreover, cyclosporin A rescued B104 cells from this lethal signal, via surface IgM, suggesting that the intracellular mechanisms involved are quite similar to those of T cell death. DNA fragmentation, which has been reported in TCR/CD3 complex-mediated T cell death, apoptosis, was not involved in the B104 cell death process, but the possible involvement of DNA single-strand breaks was suggested. Observations under light microscopy and transmission electron microscopy indicated that the morphologic features of dying B104 cells resembled necrosis rather than apoptosis. B104 cell death was shown to be quite distinct from that of WEHI-231 in cell death kinetics, the mode of cell death, and the response to cyclosporin A. These data collectively indicate that the death of B104 cells resulting from surface IgM cross-linking represents a hitherto undefined mode of programmed cell death.
我们在最近建立的人表面IgM+IgD+B淋巴瘤细胞系B104中研究了抗IgM抗体诱导细胞死亡的机制，该细胞系的生长被抗IgM抗体不可逆地抑制，但不受抗IgD抗体的影响。我们将其与通过TCR/CD3复合物介导的T细胞死亡以及对鼠抗IgM抗体敏感的B淋巴瘤细胞系WEHI-231的细胞死亡进行了比较。B104细胞死亡的快速时间进程及其对从头大分子合成和Ca2+内流的需求表明，抗IgM抗体诱导的B104细胞死亡是一种活跃的Ca(2+)依赖性程序性细胞死亡。此外，环孢素A通过表面IgM将B104细胞从这种致死信号中拯救出来，这表明所涉及的细胞内机制与T细胞死亡的机制非常相似。在TCR/CD3复合物介导的T细胞死亡（凋亡）中报道的DNA片段化并不参与B104细胞死亡过程，但提示可能涉及DNA单链断裂。光学显微镜和透射电子显微镜观察表明，濒死B104细胞的形态特征类似于坏死而非凋亡。结果表明，B104细胞死亡在细胞死亡动力学、细胞死亡模式以及对环孢素A的反应方面与WEHI-231截然不同。这些数据共同表明，表面IgM交联导致的B104细胞死亡代表了一种迄今未定义的程序性细胞死亡模式。
