HYPERSENSITIVITY TO RAPAMYCIN OF BJAB B-LYMPHOBLASTOID-CELLS

Proliferation of the BJAB B-lymphoblastoid cell line was rapidly and a lmost completely suppressed by picomolar concentrations of the immunos uppressive macrolide rapamycin (50% inhibitory concentration 10-20 pM for cells reactivated from stationary phase). This cell line was consi derably more sensitive to rapamycin than any other B-lymphoblastoid ce ll line tested, the Jurkat T-cell line or the HL60 promyelocytic cell line. BJAB cell proliferation was not affected by the related immunosu ppressive macrolides FK506 or L-685,818, which bind to the immunophili n FKBP12 competitively with rapamycin and also inhibit its peptidylpro lyl cis-trans isomerase activity. Excess FK506 or L-685,818 added simu ltaneously competitively antagonized rapamycin's anti-proliferative ac tion. 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 si gnalling system targeted by the rapamycin-FKBP12 complex, and may prov ide a model system for elucidating the role played by this pathway in lymphocyte activation. The proliferation of BJAB cells reactivated fro m stationary phase can also be used as the basis for a highly sensitiv e bioassay for the presence of rapamycin in culture media or other bio logical fluids.