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Elevation of cytosolic calcium is sufficient to induce growth inhibition in a B cell lymphoma

Recently, we have described that anti‐IgM antibodies profoundly inhibited 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 intracellular Ca2+ induced by the inhibitory concentrations of ionomycin were comparable to those in anti‐IgM‐treated cells. The growth inhibition caused by ionomycin was reversed by phorbol 12‐myristate 13‐acetate and lipopolysaccharide. In addition, the immunosuppressants, cyclosporin A and FK506 conferred significant protection from the negative signal induced by ionomycin. However, either cyclosporin A, FK506 or lipopolysaccharide was not found to have direct effect on ionomycin‐induced Ca2+ mobilization in BKS‐2 cells. Also, ionomycin augmented the anti‐IgM‐induced growth arrest in these cells. Furthermore, BKS‐2 cells that were exposed to anti‐IgM or ionomycin underwent apoptosis as characterized by DNA fragmentation. Thus, the characteristics of growth inhibition 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 was sufficient to inhibit the growth of some B lymphoma cells.