IDENTIFICATION OF IMMUNOSUPPRESSANT-INDUCED APOPTOSIS IN A MURINE B-CELL LINE AND ITS PREVENTION BY BCL-X BUT NOT BCL-2
IDENTIFICATION OF IMMUNOSUPPRESSANT-INDUCED APOPTOSIS IN A MURINE B-CELL LINE AND ITS PREVENTION BY BCL-X BUT NOT BCL-2
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DOI：
10.1073/pnas.91.15.7350
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发表时间：
1994-07-19
影响因子：
11.1
通讯作者：
QUINTANS, J
中科院分区：
文献类型：
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作者：
GOTTSCHALK, AR;BOISE, LH;QUINTANS, J
环孢菌素A、FK-506和雷帕霉素是免疫抑制剂，常用作研究淋巴细胞活化和生理性细胞死亡（PCD）的药理学探针。因为已知环孢菌素A和FK-506可以防止T细胞杂交瘤和胸腺细胞中的PCD，所以我们使用这些试剂以及雷帕霉素来确定它们是否改变导致小鼠WEHI-231细胞在表面IgM交联后凋亡的途径。我们观察到免疫抑制剂本身诱导WEHI-231细胞的PCD，但仅在对抗IgM介导的凋亡敏感的亚系中。PCD之前生长停滞，其特征在于典型的细胞凋亡的DNA片段化模式。在抗免疫球蛋白和免疫抑制剂诱导的PCD，环孢菌素A，FK-506，和雷帕霉素的B细胞系引起生长停滞。PCD也诱导蛋白质合成的抑制剂在WEHI-231细胞，但不是在成熟的B细胞系BAL-17。bcl-x（L）的过表达可阻止免疫抑制剂和蛋白合成抑制剂诱导的细胞程序性死亡，但不能阻止细胞生长停滞，而转染bcl-2则不影响细胞周期停滞的程序性死亡。这些结果表明，bcl-2和bcl-x（L）可能控制部分独立的系统来抑制淋巴细胞中的PCD，并且B和T细胞中的PCD可能受到差异调节，
Cyclosporin A, FK-506, and rapamycin are inmunosuppressants often used as pharmacological probes to study lymphocyte activation and physiological cell death (PCD). Because cyclosporin A and FK-506 are known to prevent PCD in T-cell hybridomas and thymocytes, we used these reagents, as well as rapamycin, to determine whether they alter the pathway leading to apoptosis in murine WEHI-231 cells following surface IgM cross-linking. We observed that the inmunosuppressants themselves induced PCD in WEHI-231 cells, but only in sublines susceptible to anti-IgM-mediated apoptosis. PCD was preceded by growth arrest and characterized by the DNA fragmentation pattern typical of apoptosis. In B-cell lines resistant to anti-immunoglobulin- and immunosuppressant-induced PCD, cyclosporin A, FK-506, and rapamycin caused growth arrest. PCD was also induced by inhibitors of protein synthesis in WEHI-231 cells but not in the mature B-cell line BAL-17. Immunosuppressant-induced and protein synthesis inhibitor-induced PCD, but not growth arrest, could be prevented by the overexpression of bcl-x(L), while transfection with bcl-2 did not affect PCD of cell cycle arrest. These results suggest that bcl-2 and bcl-x(L) may control partially independent systems to inhibit PCD in lymphoid cells and that PCD in B and T cells may be differentially regulated,