Induction or suppression of a B cell-specific response to self antigen in vivo is dependent upon dendritic cell activation via the TNF-alpha receptorat the time of antigen uptake

In this study we show that the retinal autoantigen, S-antigen, contains a f unctional TNF-alpha homologous domain which stimulates maturation and diffe rentiation of cultured dendritic cells (DC) or tissue DC via the p55 TNF-al pha receptor. Tissue DC became more dendritiform in shape, and migrated int o culture supernatant. S-antigen also stimulated accumulation of cell surfa ce MHC class II antigen with a corresponding loss of acidic intracellular v esicles, and induced IL-1 beta and IL-12 mRNA expression in cultured bone m arrow-derived DC. In addition, cultured splenic DC primed immune responses to S-antigen in vivo in the absence of other, exogenous cytokine sources. D C pulsed with either retinal S-antigen or another retinal autoantigen, inte rphotoreceptor retinoid binding protein (IRBP), were able to stimulate naiv e T cell proliferation in vitro, but only S-antigen-pulsed DC were able to induce an immune response in vivo and initiate antibody class switching. In contrast, IRBP-pulsed DC had no detectable in vivo priming effect and IgG antibody levels remained suppressed even after immunization with IRBP in co mplete Freund's adjuvant. These results indicate that DC from the same prec ursor population can either induce or suppress a B cell-specific response t o self antigen in vivo, the outcome being dependent upon DC activation at t he time of antigen uptake and presentation.