A cell surface antigen (BAL) defined by a mouse monoclonal antibody inducing apoptosis in a human lymphocytic...

The lack of apoptosis or programmed cell death in human tumor cells has been suggested to be one factor allowing uncontrolled growth of neoplasms. We have developed a mouse monoclonal antibody (MAb) that induces programmed cell death in a human acute leukemia cell line (KM-3) of the pre B-cell type. Stable, antibody-producing hybridomas were produced by fusing mouse myeloma cells to spleen cells from mice immunized with viable KM-3 cells. Incubation of KM-3 cells with the MAb (designated anti-BAL) resulted in growth inhibition and subsequent cell death within 2-3 days. Anti-BAL required cross-linking with a rabbit anti-mouse antibody to induce DNA fragmentation typical of apoptosis. Immunoblotting experiments with anti-BAL identified a 37-kDa protein, apparently different from any previously described apoptosis-related surface antigen. Strongest expression of the antigen was generally found on cells of lymphoid or myeloid origin. However, several other cell types such as fibroblasts and endothelial cells were also stained by anti-BAL in flow cytometry but less intensively. Despite the apparent presence of this cell surface-bound 37-kDa antigen on several normal and malignant cell types, anti-BAL induced cell death only in human malignant cell lines expressing a more immature phenotype.