An accessory role for B cells in the IL-12-induced activation of resting mouse NK cells.
IL-12 is a potent proinflammatory cytokine. The effects of IL-12 are thought to be mediated by IFN-gamma production by NK, NKT, and T cells. In this study, we show that although IL-12 stimulates NK and NK1.1(+) T cells in bulk mouse splenocytes, it does not significantly stimulate purified NK cells, indicating that other cells are required. IL-12 stimulates T cell-deficient spleen cells and those depleted of macrophages. Unexpectedly, the depletion of dendritic cells also has little effect on the stimulation of spleen cells with IL-12. In contrast, B cell depletion almost completely inhibits IL-12-induced IFN-gamma production and B cell-deficient spleen cells are poorly stimulated with IL-12. Furthermore, purified NK cells are stimulated with IL-12 in the presence of purified B cells. Thus, B cells are necessary and also sufficient for the stimulation of purified NK cells with IL-12. Whereas spleen cells from IL-18-deficient mice are not stimulated with IL-12, NK cells purified from IL-18-deficient mice are stimulated with IL-12 in the presence of wild-type (WT) B cells, and WT NK cells are not stimulated with IL-12 in the presence of IL-18-deficient B cells. Cell contact between B and NK cells is also required for IL-12-induced IFN-gamma production. Finally, B cell-deficient mice injected with IL-12 produce significantly less IFN-gamma and IL-18 in the sera than WT mice do. Thus, stimulation of NK cells with IL-12 requires B cell cooperation in vitro as well as in vivo.
Haddad
Evette A
EA
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Senger
Laura K
LK
Takei
Fumio
F
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D020382:Interleukin-18 / Q000172:deficiency; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology
D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma