FK506 inhibits anti-IgM antibody-induced apoptosis and 17 kD endonuclease activity in the human B-cell line, MBC-1, established from Burkitt's lymphoma.

Abstract

The endonuclease which causes antibody-induced apoptotic cell death in B cells is not completely understood. We previously established a B-cell line (MBC-1) from a patient with Burkitt's lymphoma at the leukaemic stage which demonstrated the typical morphology and internucleosomal 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 anti-IgM antibody. This nuclease activity was inhibited by FK506 at concentrations of 10-200 ng/ml in the active gel assay. These results raise the possibility that the 17 kD endonuclease is one of the nuclear members of the immunophilin family, which may function as an endogenous endonuclease in MBC-1 cells.