W134 - Natural Killer T Cells Promote Class-switch Recombination Towards IgG Subtypes Against T-Independent Antigens

Fernanda Aguirre-Muñoz – Institute of Biomedical Sciences, Faculty of Medicine, University of Chile. Millennium Institute on Immunology and Immunotherapy; Cristián Gutiérrez-Vera – Institute of Biomedical Sciences, Faculty of Medicine, University of Chile. Millennium Institute on Immunology and Immunotherapy; Leandro Carreño – Associate Professor, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile. Millennium Institute on Immunology and Immunotherapy

Abstract Text: T-independent (TI) antigens such as bacterial capsular polysaccharides, among others, are known for activating “innate” B cells without help from T cells. This immune response is frequently restricted to the production of IgM isotype antibodies and does not induce a memory response. Activation of Natural Killer T (NKT) cells trough the reference ligand α-Galactosylceramide (αGC), induce the secretion of factors and cytokines, like IFN-γ and IL-4, that not only promote their differentiation into plasma cells but also induce class-switch recombination towards the production of IgG antibodies. Structural analogues of α-GalCer such as AH10-7 and OCH induce polarized secretion either towards IFN-γ or IL-4, respectively. Here we aim to evaluate the effect of AH10-7 and OCH in the process of class-switch recombination against TI antigens. We used two different TI antigens, Phosphorylcholine or NP-Ficoll, admixed either with free or liposome-contained ligands of NKT cells and administered intraperitoneally in mice. 7 days later, serum and splenocytes samples were obtained to evaluate the presence of antigen-specific antibodies by ELISA, and to evaluate the expression of IgG subtypes in B cells subsets and plasma cells trough flow cytometry. AH10-7 induced the production of IgG1 specific against the antigens, which correlated with the presence B cell and plasma cells expressing high levels of IgG1 and also IgG3. Recently we also detected that AH10-7 promoted the induction of Follicular Helper NKT cells, probably interacting with antigen-specific B cells. This work supports the use of glycolipid ligands as adjuvants against T-independent antigens such as those from pathogens.