Modulation of chronic lymphocytic leukemia cells by phorbol ester: increase in Ia expression, IgM secretion and MLR...

When cultured with 12-O-tetradecanoylphorbol 13-acetate (TPA) at a concentration of 1.6 X 10(-7) M, chronic lymphocytic leukemia (CLL) cells differentiated into mature cells of B lineage and increased their expression of surface Ia antigens when compared with cells cultured in the absence of TPA. Concurrently, TPA enhanced the ability of CLL cells to stimulate in a mixed lymphocyte reaction (MLR). The events induced in vitro by TPA that are characteristic of B cell maturation included morphologic changes, reduction in surface immunoglobulin (Ig), appearance of cytoplasmic Ig, and secretion of IgM. The increase in Ia expression and the enhanced capacity to stimulate in an MLR after incubation with TPA might also be associated with maturation of the CLL cells. The changes induced in vitro by TPA in neoplastic B cells provide new information concerning the terminal events in normal B cell differentiation.