The role of calcium ions in initiating transformation of lymphocytes.

Abstract

TRANSFORMATION of lymphocytes by antigens and by nonspecific mitogens (lectins and anti-immunoglobulin sera) is a consequence of the binding of the mitogen to specific receptors on the cell surface1–3. The receptors rapidly form clusters (‘patches’) which may aggregate into polar ‘caps’4 at higher mitogen concentration. These events initiate a series of biochemical changes—enhanced uptake of ions and metabolites1, increased cyclic GMP5, and increased metabolism of phosphatidyl inositol and other phospholipids (ref. 6 and V. C. M., M. J. Hayman and M. J. C., unpublished)—which culminate in DNA synthesis and mitosis 48–72 h later. Although the sequence, relative importance and control of these events is not yet defined, there is evidence for a primary role for Ca2+. Phaseolus vulgaris phytohaemagglutinin (PHA) initiates a slow accumulation of Ca2+ by lymphocytes7,8 and its stimulation of DNA synthesis is inhibited by citrate9, EDTA (ref. 9) or EGTA (ref. 10). The inhibition is reversed by Ca2+. It has also been shown that inhibition by the low concentrations (1.4 mM) of EGTA used did not prevent binding of PHA (ref. 11). Although these results showed Ca2+ to be an important factor in initiation of transformation it was not clear whether influx of Ca2+ was the only or even the main consequence of the binding of PHA.