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.
Gagro
A
A
The Medical Research Council Centre for Immune Regulation, The University of Birmingham, The Medical School, Birmingham, GB.
Gordon
J
J
D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008211:Lymphocyte Cooperation; D014066:Palatine Tonsil; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D019013:CD40 Antigens; D016207:Cytokines; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma