An alternate B cell activation mechanism mediated by macrophages through the release of cyclo-oxygenase pathway products and interleukin 1

: The lymphokines Interleukin 1 and 2 play essential roles in the generation of antibody to artificial and natural red cell bound antigens. Critical for the appropriate function of these lymphokines is the concentration of cAMP in responding B lymphocytes. Antigen-reactive B cells mount a strong immune response in the presence of IL-1 and IL-2 when their cAMP is high, but become unresponsive when their cAMP is low. We show here that reagents which raise cAMP concentrations (Prostaglandin E, cholera toxin, forskolin) synergize strongly with IL-1 and IL-2 in the generation of antibody. We searched for physiological signals which synergize with IL-1 and IL-2 in a similar fashion and found that peritoneal macrophages facilitate strong antibody production by B cells. This helper effect is blocked by indomethacin, suggesting that it is mediated by the cyclo-oxygenase pathway and prostaglandin. Helper T cells can also complement IL-1 and IL-2 in stimulating B cells to produce antibody. This effect is not blocked by indomethacin.