INTERACTION OF POKEWEED MITOGEN WITH MONOCYTES IN THE ACTIVATION OF HUMAN-LYMPHOCYTES

Abstract

The role of monocytes in the in vitro activation of human T cells and B cells by pokeweed mitogen (PWM) was examined. The T cell-dependent PWM-induced B cell activation process was monocyte-dependent. Fluorescence-activated cell sorter analysis revealed that upon addition to peripheral blood mononuclear cells, fluoresceinated PWM, at concentrations that provided optimal B cell and T cell activation, bound predominantly to human monocytes. The binding of PWM to monocytes was reversible and could be displaced within the first few hours of binding by oligomers of N-acetylglucosamine (GLcNAc). As a functional correlate of the binding studies, it was shown that PWM-pulsed monocytes could induce B lymphocytes to become plaque-forming cells (PFC) and T lymphocytes to undergo proliferation. Markedly reduced PFC and blastogenic responses were observed when monocyte-depleted B lymphocytes and T lymphocytes were respectively pulsed with PWM and washed, followed by the addition of non-PWM-pulsed monocytes to the cultures. The initial event in the PWM-induced activation of human lymphocytes, for both in vitro T lymphocyte blastogenic responses and B lymphocyte Ig secretion, appears to be binding of the mitogen to sugar residues on the surface membrane of the monocyte, followed by subsequent interaction with the appropriate lymphocytes. The processs of PWM binding to monocytes did not appear to affect the baseline production of interleukin-1 by human monocytes, nor could soluble factors from PWM-pulsed monocytes substitute for intact cells in the initiation of the lymphocyte activation process.