Tumor promotor phorbol myristic acetate is a T-cell-dependent inducer of immunoglobulin secretion in human lymphocytes

Abstract

Human peripheral blood mononuclear cells were induced by 10 to 200 ng/ml phorbol myristic acetate (PMA) to secrete immunoglobulin (Ig). Using protein A-RBC plaque formation to detect secreting cells (PFC), Day 5 and Day 7 PFC induced by PMA were 0.2 to 1.4% of initial numbers of cultured cells. In parallel cultures, pokeweed mitogen (PWM) induced PFC corresponding to 1–3% and 0.6–8% of initial cell numbers, respectively. Suppressor cells for Ig secretion purifying with T (E-rosetting) cells were found in most donors. These were sensitive to mitomycin C. In some donors, PFC responses could only be detected after removal of suppressor cells. By double separation of T cells from B cells, the PMA response was shown to be dependent on T helper cells, similarly to PWM. This is in contrast to a 20-fold stimulation of Ig secretion in some human B culture lines by PMA alone. PMA is thus a T-dependent polyclonal activator for resting, blood B lymphocytes, and a direct stimulator of Ig production in certain dividing lymphoblasts represented by B-cell lines.