FK506 INHIBITS ANTI-IGM ANTIBODY-INDUCED APOPTOSIS AND 17KD ENDONUCLEASE ACTIVITY IN THE HUMAN B-CELL LINE, MBC-1, ESTABLISHED FROM BURKITTS-LYMPHOMA

The endonuclease which causes antibody-induced apoptotic cell death in B cells is not completely understood. We previously established a B-c ell line (MBC-1) from a patient with Burkitt's lymphoma at the leukaem ic stage which demonstrated the typical morphology and internucleosoma l DNA fragmentation of apoptotic cell death when treated with anti-IgM antibody. FK506, an immunosuppressive agent and calcineurin inhibitor , partially rescued the anti-IgM antibody-induced cell death in these MBC-1 cells. DNA SDS-PAGE nuclease activity assay demonstrated that a 17 kD protein exhibited endonuclease activity. Active gel assay showed nuclease activity in the cellular nuclear extract not treated with an ti-IgM antibody. This nuclease activity was inhibited by FK506 at conc entrations of 10-200 ng/ml in the native gel assay. These results rais e the possibility that the 17 kD endonuclease is one of the nuclear me mbers of the immunophilin family, which may function as an endogenous endonuclease in MBC-1 cells.