Suppression of immunoglobulin synthesis by activated B cells in chronic active liver diseases and primary biliary cirrhosis.

We investigated the suppressor function of peripheral blood B cells from patients with chronic active liver diseases (CALD) and primary biliary cirrhosis (PBC). Suppressor cells were generated by preincubation of B cells with protein A, and suppressive effects were evaluated by inhibition of pokeweed mitogen-induced immunoglobulin (Ig) synthesis of normal peripheral blood lymphocytes (PBL) in second-set cultures. The mean percent suppressions for IgG and IgM synthesis of 12 HBsAg-negative patients with CALD, who were not on prednisone therapy, were lower (p less than 0.01, respectively) than those of controls. B cells from 6 HBsAg-positive patients with CALD also showed less suppression of IgG and IgM synthesis (p less than 0.01, respectively). Moreover the suppression for IgG and IgM in 7 patients with PBC were decreased (p less than 0.01, respectively). There was an inverse correlation between serum gammaglobulin level and percent suppression for IgG synthesis by protein A-activated B cells of patients with CALD (r = -0.50, p less than 0.05). Further studies demonstrated that protein A-activated B cells were capable of activating the suppressor function of T cells, which could then act to inhibit further B cell differentiation. These results suggest an aberrance of a feedback mechanism that is likely to regulate Ig synthesis in patients with CALD and PBC.