Enhancement of Anti‐tumor Activity of Natural Killer Cells by BALL‐1, a B Cell Lymphoma Line

The anti‐tumor activity of human peripheral blood mononuclear cells (PBMC) against various tumor cell line cells (K562, Daudi, KMG‐2, and KATOIII) was enhanced by coculture with irradiated BALL‐1, but not with other irradiated B cell line cells (NALM‐1, Namalwa, and Daudi). PBMC cocultured with BALL‐1, however, failed to exhibit evident cytotoxicity against autologous concanavalin A‐induced lymphoblasts. The enhancement of the anti‐tumor activity seemed not to be correlated with EBNA and HLA‐DR expression on B cell line cells. Monoclonal antibodies (mAbs) against interleukin (IL)‐2, interferon‐γ, IL‐12, IL‐15, tumor necrosis factor‐α and lymphotoxin showed little or no suppression of the anti‐tumor activity of PBMC treated with irradiated BALL‐1. Furthermore, the culture supernatants of BALL‐1 failed to enhance the anti‐tumor activity of PBMC, suggesting no involvement of soluble factors in the induction of the anti‐tumor activity. The anti‐tumor activity of PBMC treated with BALL‐1 was synergistically enhanced by an additional IL‐2 stimulation. Periodate‐lysine‐paraformaldehyde‐fixed, but not ethanol‐ or acetone‐fixed, BALL‐1 could significantly enhance the anti‐tumor activity. Furthermore, BALL‐1‐derived membrane fraction, but not that of Daudi, enhances the anti‐tumor activity. It was thus suggested that some membrane glycoproteins on the cell surface of BALL‐1 play a crucial role in the induction of the anti‐tumor activity. By analysis using mAbs against human leukocytes, we found that depletion of CD11b, CD16, and CD56‐positive cells resulted in decreased anti‐tumor activity, suggesting that the main effector cells in the BALL‐1‐induced anti‐tumor activity were natural killer (NK) cells. The present results thus raise the possibility that BALL‐1, probably via membrane glycoproteins, modulates NK cell‐mediated anti‐tumor activity.