REGULATION OF HUMAN-IGG SUBCLASS PRODUCTION BY CYTOKINES - HUMAN-IGG SUBCLASS PRODUCTION ENHANCED DIFFERENTIALLY BY INTERLEUKIN-6

Peripheral blood mononuclear cells (PBMC) stimulated with pokeweed mitogen (PWM) produced increased IgG when cultured with interleukin-6 (IL-6). IgG subclass analysis showed that the presence of IL-6 during the last half of the culture period enhanced IgG1 and IgG4 production. Enhancement of IgG2 synthesis required the presence of IL-6 solely during the last half of the culture period, whereas enhancement paradoxically was blocked by its presence during the first half. The IgG3-enhancing effect of IL-6 was observed only when IL-6 was present throughout the culture period. The critical role of IL-6 was supported by the inhibition of IgG subclass synthesis by anti-IL-6 antibody. PBMC depleted of cells bearing surface IgG of a particular subclass did not synthesize that subclass. This non-responsiveness, which was not reversed even by an addition of IL-6, indicates that the main action of IL-6 is on the differentiation of committed B cells. In addition, IL-6 triggered T cells to produce significant helper activity. These results indicate that IL-6 enhances IgG subclass production differentially and that its critical role in IgG subclass synthesis is in part mediated by T cells, as well as by its direct action on B cells. These findings should be useful for analysing such immune disorders as IgG subclass deficiencies and autoimmune diseases.