B-T cell interactions modulate inhibitory effects of interleukin-4 on human B cell proliferation

In this study, we investigated the role of B-T cell contacts in interleukin Ia-mediated inhibition of human B lymphocyte proliferation induced by mitogenic doses of soluble anti-mu monoclonal antibody (mAb). We show that additional cross-linking of B cell antigens, using Sepharose beads coated with anti-mu, anti-(IL)-4 mAb (but not soluble mAb) or anti-CD40 antigen counteracted the inhibitory activity of IL-4. More importantly, cell contacts between B cells and activated T cells (but not unstimulated T cells) were sufficient to counteract IL-4-mediated inhibition of DNA synthesis. In addition, the inhibitory activity of IL-4 on chronic lymphocytic leukemia B cells stimulated with anti-mu and IL-2 was itself reduced by the presence of fixed activated T cells. Our data suggest that a major role for IL-4 would be to prepare B cells to receive additional mitogenic signals through cell contact interactions with activated T lymphocytes. When such interactions do not occur IL-4 may block DNA synthesis, preventing uncontrolled B cell proliferation.