The interplay between T helper subset cytokines and IL-12 in directing human B lymphocyte differentiation

This study asks how T helper (TH) subset cytokines impact upon IL-12-directed change in B cells engaged in signaling via the B cell receptor and CD40, essential components in the initiation of T-dependent B cell responses. For B cells stimulated in this way, IL-12 promoted a distinct phenotype highlighted by the hyper-expression of CD38: the Th1 cytokine IFN-gamma reproduced the IL-12 effects while neutralizing antibody to IFN-gamma reversed IL-12-dependent change. The divergent pathway of differentiation promoted by the Th2 cytokine IL-4 (characterized by hyper-induction of CD23) was left unchecked by IL-12. IL-10 was found to dampen IL-12 actions by suppressing IL-12-dependent IFN-gamma production but failed to perturb the effects of exogenous IFN-gamma. Thus, IL-12--by invoking autocrine IFN-gamma production--promotes phenotypic deviation in B cells engaging T-dependent signals. The reversal of such Th1 driving of B cells by IL-10 only when the source of IFN-gamma is endogenous and the inability of IL-12 to impact upon IL-4-directed differentiation suggest a progressive and hierarchical commitment of B cells to polarization during a developing T-dependent response dominated at the level of the Th cell rather than that of the dendritic cell.