The requirement for high intracellular cyclic adenosine monophosphate concentrations distinguishes two pathways of B cell activation induced with lymphokines and antibody to immunoglobulin

Abstract

Mouse B lymphocytes proliferate when stimulated with anti-IgM and the lymphokines B cell-stimulating factor-1 (BSF-1) interleukin (IL)-4 and IL-1. We show herein that two anti-IgM-stimulated B cell responses can be distinguished by their sensitivity to cyclic adenosine monophosphate (cAMP). cAMP inhibits B cell proliferation facilitated by BSF-1 and enhances the B cell response facilitated by IL-1. IL-1 and BSF-1-dependent B cell responses are additive, suggesting that distinct B cell subpopulations are involved. BSF-1-reactive B cells are not inhibited by cAMP in the presence of IL-1. This suggests that IL-1 determines whether cAMP, which has elsewhere been shown to cause nuclear translocation of protein kinase C in resting B cells, inhibits or enhances B cell responses. Comparative studies suggest that the IgM response of spleen cells to red cell-bound antigen involves one of the two pathways described, namely the one that involves IL-1 and cAMP. BSF-1 has no noticeable effect on a Mishell-Dutton plaque-forming cell response. In view of literature on the facilitation by BSF-1 of the IgG response, we consider the possibility that IL-1 functions to stir B cells into an IgM response, whereas BSF-1 acts on B cells that are poised to become IgG producers.