Figure 6. TLR7 overexpression induces pathogenic autoantibodies in Sle1 TNF^–/– mice.

(A) Survival plots of male Sle1 mice of the indicated genotypes. Log-rank test **P < 0.01. (B–D) Plots show relative units of IgG antibodies against cardiolipin (B), DNA (C), and Sm/RNP (D) from sera of male Sle1 mice of the indicated genotype at 3, 6, and 9 months of age. (E–H) Summary bar graphs of flow cytometry analysis. (E and F) Percentage and count of CD95⁺GL7⁺ cells in CD19⁺ B cells from male Sle1, Sle1 Yaa, Sle1 TNF^–/–, and Sle1 Yaa TNF^–/– mice. (G and H) Percentage of PNA⁺CD38^– (G) and Ki67⁺Bcl6⁺ (H) cells in splenic CD95⁺GL7⁺ B cells. (I) Immunohistochemistry images (original magnification, 20×) show Ki67⁺Bcl6⁺ B cells in GCs of male Sle1 (top left) and Sle1 Yaa (bottom left) mice. Ki67⁺Bcl6⁺ B cells are located at the T-B border in the T cell zone of male Sle1 TNF^–/– (top right) and Sle1 Yaa TNF^–/– (bottom right) mice (representative of 3–4 mice per group). (J) Ki67⁺ cells are located in GCs in Sle1 Yaa mice and at the T-B border and in the bridging zones adjacent to extrafollicular foci in Sle1 Yaa TNF^–/– mice. (K) Pie charts show mutation frequencies in VH sequences from CD138⁺ PCs from Sle1 Yaa (left) and Sle1 Yaa TNF^–/– (right) mice. χ², ****P < 0.0001. (L and M) Percentage and count of CD19⁺CD11c⁺ age-associated B cells (ABC) in male Sle1, Sle1 Yaa, Sle1 TNF^–/–, and Sle1 Yaa TNF^–/– mice. (N and O) Percentage and number of CCR6⁺CD38⁺ memory B cells in Sle1 Yaa and Sle1 Yaa TNF^–/– mice. Dots on bar graphs represent individual mice. Immunohistochemistry representative of 3–5 mice per group. (B–H, L, and M) ANOVA Kruskal-Wallis with Dunn’s multiple comparisons test, *P < 0.05: **P < 0.01, ***P < 0.001. (N and O) Mann-Whitney nonparametric test.