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

Abstract

In this study we show that the retinal autoantigen, S-antigen, contains a functional TNF-alpha homologous domain which stimulates maturation and differentiation of cultured dendritic cells (DC) or tissue DC via the p55 TNF-alpha receptor. Tissue DC became more dendritiform in shape, and migrated into culture supernatant. S-antigen also stimulated accumulation of cell surface MHC class II antigen with a corresponding loss of acidic intracellular vesicles, and induced IL-1beta and IL-12 mRNA expression in cultured bone marrow-derived DC. In addition, cultured splenic DC primed immune responses to S-antigen in vivo in the absence of other, exogenous cytokine sources. DC pulsed with either retinal S-antigen or another retinal autoantigen, interphotoreceptor retinoid binding protein (IRBP), were able to stimulate naive 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 complete Freund's adjuvant. These results indicate that DC from the same precursor population can either induce or suppress a B cell-specific response to self antigen in vivo, the outcome being dependent upon DC activation at the time of antigen uptake and presentation.