Regulatory role of circulating monocytes in the differentiative and proliferative responses of human B lymphocytes

Abstract

Depletion of monocytes from peripheral blood mononuclear cells had a profound influence on mitogen- and antigen-induced B-cell proliferation and differentiation to antibody-secreting cells. Such depletion enhanced the generation of plasma cells identifiable by immunofluorescence and specific plaque-forming cells (PFC) against sheep erythrocytes in cultures containing pokeweed mitogen, staphylococcal protein A (SPA), concanavalin A (Con A), and phytohemagglutinin (PHA). This enhancement was especially marked in the cases of SPA and Con A. Without monocyte depletion only 0.1 to 0.4% of the cultured cells were shown to be plasma cells and as much as a 100-fold increase was seen with monocyte removal. Similar results were also obtained in the PFC assay. These studies suggest that Con A, SPA, and PHA may be considered as inducers of B-cell differentiation to plasma cells under appropriate conditions. In two B-cell differentiation systems initiated by antigen involving allogeneic helper cells and autologous helper factors, the monocyte-dependent inhibition was also demonstrated. In addition, monocyte depletion enhanced proliferation of B cells in the presence of irradiated autologous T cells and pokeweed mitogen. This enhancement was also seen when B cells were stimulated to divide by purified anti-μ antibodies. The addition of adherent cells to monocyte-depleted cultures confirmed the suppressive effect of excessive monocytes but also demonstrated that the presence of a certain number of monocytes was necessary for optimal responses in at least some of the systems studied. The striking effect of monocytes in these different systems emphasizes the importance of their consideration in B-cell stimulation studies, especially those involving human peripheral blood.