Suppression of polyclonal immunoglobulin biosynthesis by a soluble factor: T-cell dependent and T-cell independent mitogens.

When normal human spleen cells are pulsed with concanavalin A (Con A), a portion become suppressor cells which in co-culture can inhibit immunoglobulin synthesis by other normal spleen cells stimulated by pokeweed mitogen (PWM). One mechanism whereby these Con-A activated spleen cells suppress Ig synthesis appears to be by the secretion of a soluble suppressor factor(s) since supernatants of Con-A stimulated splenocytes also suppress the polyclonal synthesis of immunoglobulin by human spleen cells. In this study, we report that supernatants of Con-A activated spleen cells suppress the in vitro synthesis of IgG, IgM and IgA by human spleen cells cultured with PWM. Our results indicate that the soluble suppressor factor(s) blocks an early stage in the differentiation of B lymphocytes into plasma cells without affecting the synthesis and secretion of immunoglobulin by more mature lymphocytes which appear to be irreversibly committed toward the pathway of synthesizing immunoglobulin. In addition, we studied the ability of normal human spleen cells to synthesize polyclonal immunoglobulin when cultured with either the T-cell dependent PWM or T-cell independent mitogens lipopolysaccharide (LPS) and Nocardia. Our results demonstrate that normal human splenic mononuclear cells cultured with either Nocardia, LPS or PWM are significantly stimulated to synthesize polyclonal IgG, IgM and IgA. Furthermore, supernatants of Con-A activated human spleen cells suppressed the polyclonal synthesis of these three antibody classes by human spleen cells responding to either T-cell dependent or independent mitogens.