Dendritic cell-derived IL-12 promotes B cell induction of Th2 differentiation: a feedback regulation of Th1 development.
B cells convert what are normally conditions for Th1 differentiation into an environment suitable for Th2 development. This capacity is dependent on CD40 as B cells from CD40-/- mice do not elicit Th2 differentiation. To elucidate the basis of this effect, we surveyed cytokine RNA made by naive B cells after activation with anti-Ig and anti-CD40. Resting B cells make TGF-beta message only, however, 4 days after activation, RNA encoding IL-6, IL-10, and TNF-alpha was found. The expression of these messages was accelerated by 2 days in the presence of IL-12. The relevance of these observations to T cell differentiation was investigated: addition of OVA peptide to splenic cells from DO.11.10 transgenic mice causes most T cells to make IFN-gamma. Coactivation of B cells in these cultures reduces the number of IFN-gamma-producing T cells and increases the number synthesizing IL-4. Abs to IL-6 and IL-10 block the IL-4 enhancement. Dissection of the component APC demonstrated that interaction of B cells with IL-12-producing dendritic cells is crucial for B cell-mediated IL-4 enhancement: Thus, B cells preactivated in the presence of dendritic cells from IL-12-/- mice show little IL-4-inducing activity when used to activate T cells. This immune regulation is initiated by IL-12 and therefore represents a feedback loop to temper its own dominant effect (IFN-gamma induction).
Skok
J
J
Department of Immunology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
Poudrier
J
J
Gray
D
D
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002474:Cell-Free System / Q000276:immunology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D015536:Down-Regulation / Q000276:immunology; D005246:Feedback / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism; D015850:Interleukin-6 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology
D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D017077:Culture Media, Conditioned; D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4