Partial protection from lupus-like disease in B-cell specific IFNAR-deficient B6.Nba2 mice

Abstract

Abstract A majority of patients presenting with systemic lupus erythematosus (SLE) have increased serum concentrations of interferon alpha (IFNα). IFNα has previously been shown to affect lymphocyte activities such as B cell differentiation and T cell maintenance, but whether IFNα signaling specifically in B cells is required for disease pathology remains unknown. In order to examine the role of IFNα stimulation on B cells, we backcrossed mice lacking the IFNα receptor on B cells, Mb1.cre IFNARflx/flx, with the B6.Nba2 lupus mouse model. B6.Nba2.BΔIFNAR mice were evaluated alongside littermate control mice for splenomegaly, abnormal spleen subset distribution, IgG immune-complex deposition in the kidney glomeruli. Serum total IgM, total IgG and anti-chromatin IgG levels were determined monthly. BΔIFNAR mice display normal IgM and IgG levels, but decreased serum antinuclear autoantibody levels (p<0.05), while deposition of IgG immune complexes in kidney glomeruli was similar to that of control mice. Both spleen weight and total splenocyte number were found to be significantly decreased in BΔIFNAR mice (p<0.05). Analyses of spleen cell subsets at 4 months of age revealed a trend towards decreased plasma cells and GC B cells in spleens of BΔIFNAR mice. Despite IFNAR being removed from B cells only, we observed a shift in the balance of effector/memory to naïve CD4 T cells in BΔIFNAR mice. In summary, we found that B6.Nba2.BΔIFNAR mice were partly protected from lupus pathology including splenomegaly, autoantibody production and B cell hyperactivation. Most surprisingly, T cell activation appeared to be diminished in B6.Nba2.BΔIFNAR mice, suggesting that B cells play a central role as both APCs and ASCs in the B6.Nba2 mouse model of lupus.