ELEVATION OF CYTOSOLIC CALCIUM IS SUFFICIENT TO INDUCE GROWTH-INHIBITION IN A B-CELL LYMPHOMA

Recently, we have described that anti-IgM antibodies profoundly inhibi ted the growth of BKS-2, an immature B cell lymphoma. In this report, we demonstrated that ionomycin alone at very low concentrations (20 nm ) inhibited the growth of BKS-2 cells completely. The levels of intrac ellular Ca2+ induced by the inhibitory concentrations of ionomycin wer e comparable to those in anti-IgM-treated cells. The growth inhibition caused by ionomycin was reversed by phorbol 12-myristate 13-acetate a nd lipopolysaccharide. In addition, the immunosuppressants, cyclospori n A and FK506 conferred significant protection from the negative signa l induced by ionomycin. However, either cyclosporin A, FK506 or lipopo lysaccharide was not found to have direct effect on ionomycin-induced Ca2+ mobilization in BKS-2 cells. Also, ionomycin augmented the anti-I gM-induced growth arrest in these cells. Furthermore, BKS-2 cells that were exposed to anti-IgM or ionomycin underwent apoptosis as characte rized by DNA fragmentation. Thus, the characteristics of growth inhibi tion induced by ionomycin and anti-IgM appeared to be similar in that phorbol 12-myristate 13-acetate, lipopolysaccharide, cyclosporin A and FK506 caused significant reversal from such negative signals and both ionomycin and anti-IgM induced apoptosis in these cells. Altogether, these results showed that the elevation of intracellular Ca2+ alone wa s sufficient to inhibit the growth of some B lymphoma cells.