Figure 2.

The contribution of IRF7 to a TLR7-driven FcγRIIB −/− model of SLE. (A–H) B and T cell responses were evaluated in the spleens of FcγRIIB−/−yaa (RIIB−/−yaa) and FcγRIIB−/−yaaIRF7−/− (RIIB−/−yaaIRF7−/−) mice at 2 and 4 mo of age. (A) Spleen weight of RIIB−/−yaa and RIIB−/−yaaIRF7−/− mice. (B and C) (B) Flow cytometry gating strategy and (C) frequency and number of B220+GL-7+CD95+ GC B cells of total B220+ B cells. (D and E) (D) Number and (E) flow cytometry gating strategy and frequency of CD138+TACI+ PCs in IgD B cells. (F) Frequency of IgDCD11b+CD11c+ ABCs of B220+CD19+ B cells in the spleen. (G and H) Frequency of (G) CD4+CD44+CD62L Teffs of total CD4+ cells and (H) CD4+CD44+CD62LCXCR5+PD-1+ Tfh of total CD4+ cells. (I) Serum IgG and IgG2c anti-SmRNP antibodies were measured by ELISA. (J and K) High-dimensional flow cytometry analysis of kidney immune cell infiltrates identifying following populations: total CD45+ cells, CD45+CD11bCD19+B220+ B cells, CD45+CD19CD11bCD11c+B220+CD317+ pDCs, CD45+CD19B220CD56CD11b+CD11c+MHCIIhi iDCs, CD45+CD19B220CD56CD11b+CD11c+Ly6c+Ly6G moDCs, CD45+CD19B220CD56CD11bCD11c+MHCII+ cDCs, CD45+CD19B220CD56CD11b+Ly6C+Ly6G monocytes, CD45+CD19B220CD56CD11b+Ly6C+Ly6G+ neutrophils, CD345+B220CD19CD56CD11b+F4/80+MHCII+ macrophages, CD45+CD19B220CD11bCD4+ CD44+CD62L CD4+ Teffs, CD45+CD11bB220CD19CD4CD8CD56+ NK cells, and CD45+CD19B220CD11bCD8+CD44+CD62L CD8+ Teffs. (L and M) (L) BUN and (M) creatinine levels were measured in sera collected from 4-mo-old mice. (N) The percentage of survival in RIIB−/−yaa and RIIB−/−yaaIRF7−/− mice. Each symbol represents an individual mouse, and data are presented as means ± SEM. Data in panels A–I and N (n = 7–13 mice per group) represent three experiments. Data in panels J–M (n = 5–11 mice per group) represent two to three experiments. P values were calculated via two-way ANOVA with Dunn–Sidak correction (A–K), an unpaired Student’s t test (L), Mann–Whitney test (M), or log-rank (Mantel–Cox) test (N) (*, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001). NS, not significant; cDCs, conventional DCs; moDCs, monocyte-derived DCs.

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