Regulation of human IgG subclass production by cytokines. IFN-gamma and IL-6 act antagonistically in the induction of human IgG1 but additively in the induction of IgG2.

In this study, we investigated the roles of IFN-gamma and IL-6 in the induction of IgG subclasses from PBMC stimulated with PWM. The presence of IFN-gamma in the first half of the culture period dramatically suppressed the production of IgG1, whereas spontaneous IgG2 secretion was sharply enhanced by IFN-gamma when the latter was present throughout the culture period. Endogenous IFN-gamma was shown to be effective in IgG1 and IgG2 production because IgG1 production was enhanced and IgG2 production was inhibited by the addition of anti-IFN-gamma Ab. Because IFN-gamma did not act on the PBMC depleted of surface IgG2-bearing cells to enhance IgG2, IFN-gamma is unlikely to act as a switching factor. Differing from IFN-gamma, IL-6 enhanced every IgG subclass production as a nonswitching factor, although each of IgG subclasses required IL-6 differentially; maximal IgG1 responses and IgG4 responses occurred when IL-6 was present for the entire culture period or the last half of the culture period, whereas maximal IgG3 responses required the presence of IL-6 for the entire culture period and maximal IgG2 responses were seen when IL-6 was present solely during the last half of the culture period. IFN-gamma antagonized the synthesis of IgG1 by IL-6 and cooperated with IL-6 to produce IgG2. This observation was further supported by the fact that the IL-6-induced IgG1 and IgG2 enhancement were respectively up-regulated and down-regulated by anti-IFN-gamma. Altogether, the critical roles of IFN-gamma and IL-6 were implicated.