INCREASED EXPRESSION OF IFN-ALPHA AND IL-6 BY HYPERACTIVE PLASMACYTOID DENDRITIC CELLS IN BXD2 AUTOIMMUNE MICE (130.25)

Abstract

Abstract BXD2 is a mouse model which exhibits several features of human SLE and arthritis. IFN-α is a known cytokine which promotes B-cell maturation and antibody CSR and SHM. ELISA results of in vitro culture of spleen cells demonstrates that IFN-α expression reaches a peak at 2 months of age (4-fold increase compared to nonautoimmune mice; p<0.005), suggesting that IFN-α can serve as an early trigger for B-cell autoimmunity. Immunofluorescent staining for CD11c+ antigen-presenting cells identifies an increased population (2–4 fold; p<0.005) of plasmacytoid dendritic cells (pDCs). Flow cytometry results demonstrate splenic pDCs are the primary cells which express IFN-α (>80%) and IL-6 (>96%) in BXD2 mice. In vivo treatment of 2 m-old BXD2 mice with DOTAP/CpG resulted in a 200-fold increase in IFN-α compared to a 4-fold increase in B6 mice. This is associated with high levels of autoantibody titers and CSR. In conclusion, BXD2 mice exhibit a significantly increased population of pDCs that express IFN-α at a young age which is associated with increased humoral response.