A phorbol ester tumor promoter induces changes in the expression of immunoglobulins and DR antigens in human lymphoblastoid cells.

The present study indicates that 12-O-tetradecanoyl phorbol 13-acetate (TPA) can induce either increases or decreases in the relative expression of membrane-associated IgM and IgD as well as the expression of other markers of lymphocyte differentiation on human B lymphoblasts, depending on the clone studied. The changes in membrane Ig expression are apparent within 24 hr and are maximal at about 48 hr after the addition of the compound. In clone BL, TPA decreases the membrane IgM/IgD ratio as determined by the percentage of cells bearing these isotypes and by their densities on single cells. In clone MW-E, TPA has the opposite effect. Although these changes are followed by an increase in Ig secretion by MW-E cells, measured by immunofluorescence and the protein A plaque assay, there is no induction of Ig secretion in BL cells. In addition, TPA increases the expression in BL of an additional B lymphocyte marker, the D region-related (DR) antigens, while having the opposite effect in MW-E. In two sublines of Daudi, a membrane IgM-positive, IgD-negative, nonsecreting cell line, TPA treatment resulted in the expression of membrane IgD without the induction of Ig secretion. Thus, the TPA-induced changes in the IgM/IgD ratio and DR antigen expression are inversely related and are not due to differential proliferation of subpopulations. Taken together, it appears that, depending on the particular clone of B lymphoblasts studied, TPA can induce or inhibit a coherent program of B lymphocyte maturation.