Kay J E, Smith M C, Frost V, Morgan G Y
School of Biological Sciences, University of Sussex, Brighton, UK.
Immunology. 1996 Mar;87(3):390-5.
Proliferation of the BJAB B-lymphoblastoid cell line was rapidly and almost completely suppressed by picomolar concentrations of the immunosuppressive macrolide rapamycin (50% inhibitory concentration 10-20 pM for cells reactivated from stationary phase). This cell line was considerably more sensitive to rapamycin than any other B-lymphoblastoid cell line tested, the Jurkat T-cell line or the HL60 promyelocytic cell line. BJAB cell proliferation was not affected by the related immunosuppressive macrolides FK506 or L-685,818, which bind to the immunophilin FKBP12 competitively with rapamycin and also inhibit its peptidylprolyl cis-trans isomerase activity. Excess FK506 or L-685,818 added simultaneously competitively antagonized rapamycin's anti-proliferative action. Levels of FKBP12 and uptake of rapamycin from the culture medium were also normal in BJAB cells. The hypersensitivity to rapamycin of BJAB cells thus reflects an unusual dependence on the intracellular signalling system targeted by the rapamycin-FKBP12 complex, and may provide a model system for elucidating the role played by this pathway in lymphocyte activation. The proliferation of BJAB cells reactivated from stationary phase can also be used as the basis for a highly sensitive bioassay for the presence of rapamycin in culture media or other biological fluids.
皮摩尔浓度的免疫抑制大环内酯类药物雷帕霉素能迅速且几乎完全抑制BJAB B淋巴母细胞系的增殖（对于从静止期重新激活的细胞，50%抑制浓度为10 - 20皮摩尔）。该细胞系对雷帕霉素的敏感性比所测试的任何其他B淋巴母细胞系、Jurkat T细胞系或HL60早幼粒细胞系都要高得多。BJAB细胞的增殖不受相关免疫抑制大环内酯类药物FK506或L - 685,818的影响，这两种药物与免疫亲和素FKBP12竞争性结合雷帕霉素，并抑制其肽基脯氨酰顺反异构酶活性。同时添加过量的FK506或L - 685,818可竞争性拮抗雷帕霉素的抗增殖作用。BJAB细胞中FKBP12的水平以及从培养基中摄取雷帕霉素的情况也均正常。因此，BJAB细胞对雷帕霉素的超敏感性反映了其对雷帕霉素 - FKBP12复合物所靶向的细胞内信号系统的异常依赖性，并且可能为阐明该途径在淋巴细胞激活中所起的作用提供一个模型系统。从静止期重新激活的BJAB细胞的增殖也可作为一种高灵敏度生物测定法的基础，用于检测培养基或其他生物流体中雷帕霉素的存在。
