Influence of TPA (12-0-tetradodecanoyl-phorbol-13-acetate) on human B lymphocyte function

The effect of the tumour-promoting agent TPA (12-0-tetra-dodecanoyl-phorbol-13-acetate) on the proliferation and Ig secretion response of blood and tonsil lymphocytes was investigated and compared to that of the T-cell-dependent polyclonal activators pokeweed mitogen (PWM) and group A streptococcal cell membranes (A-ScM) or the T-cell-independent B cell mitogen Staphylococcus aureus Cowan I (SAC) and a T-cell-independent B cell activator Klebsiella pneumoniae (Klebs M). In blood mononuclear cells (MNC), a rather weak, monocyte-dependent DNA synthetic response was observed after exposure to TPA, in comparison to PWM, A-ScM or SAC. Whereas highly purified B cells did not respond to TPA, purified T cells proliferated to a similar degree as unseparated MNC; moreover, the addition of T to B lymphocytes enhanced proliferation rates proportionally to the number of T cells added. This suggests that TPA acts as a polyclonal T cell activator (PTA) for human blood and tonsil cells. Similarly, TPA induced only small amounts of Ig secretion in blood and in tonsil MNC, as determined by an ELISA assay, and no significant Ig secretion in highly purified B cells. The rather weak B cell differentiation response was not due to a monocyte suppressor effect, since partially monocyte-depleted MNC or B cells responded similarly to the non-depleted cells. Thus, TPA cannot be considered as an alternative to other B cells stimulators, both with regard to DNA synthesis and Ig secretion.