Extended Data Fig. 2: TLR9-MyD88 signaling promotes disease.

a-e, Evaluation of the clinical parameters separated by gender (Tlr9^−/− male, n = 21; Tlr9^P915H/P915H male, n = 37; Tlr9^+/− male, n = 24; Tlr9^−/− female, n = 22; Tlr9^P915H/P915H female, n = 25; Tlr9^+/− female, n = 28; (a, female) Tlr9^−/− versus Tlr9^P915H/P915H p = 0.0022, Tlr9^−/− versus Tlr9^+/− p = 0.0431; (b) Tlr9^−/− versus Tlr9^P915H/P915H p < 0.0001, Tlr9^P915H/P915H versus Tlr9^+/− p = 0.0005; (c) Tlr9^−/− versus Tlr9^P915H/P915H p = 0.0007, Tlr9^P915H/P915H versus Tlr9^+/− p = 0.0445; (d) Tlr9^−/− versus Tlr9^P915H/P915H p < 0.0001, Tlr9^P915H/P915H versus Tlr9^+/− p = 0.0005; (e) Tlr9^P915H/P915H versus Tlr9^+/− p = 0.0521) f, Percent TCR⁻CD19⁺ B cells of live splenocytes in male and female mice of the indicated genotypes (Tlr9^−/−, n = 36; Tlr9^P915H/P915H, n = 55; Tlr9^+/−, n = 44; Tlr9^−/− versus Tlr9^+/− p = 0.0260). g-h, Percent CD21^hi CD23^lo MZ (Tlr9^−/−, n = 36; Tlr9^P915H/P915H, n = 55; Tlr9^+/−, n = 44), and CD11b⁺ CD11c⁺ ABC of live B cells in mice of the indicated genotypes (Tlr9^−/−, n = 36; Tlr9^P915H/P915H, n = 53; Tlr9^+/−, n = 41; (g) Tlr9^−/− versus Tlr9^P915H/P915H p = 0.0109, Tlr9^P915H/P915H versus Tlr9^+/− p = 0.0032; (h) Tlr9^−/− versus Tlr9^P915H/P915H p = 0.0228). i, Percent TCR⁻CD44^hiCD138^hi plasmablasts of live splenocytes in mice of the indicated genotypes (Tlr9^−/−, n = 36; Tlr9^P915H/P915H, n = 55; Tlr9^+/−, n = 44; Tlr9^−/− versus Tlr9^P915H/P915H p = 0.0264). j, Percent TCR⁺CD4⁺ and TCR⁺CD8⁺ cells of live splenocytes in male and female mice of the indicated genotypes (Tlr9^−/−, n = 36; Tlr9^P915H/P915H, n = 52; Tlr9^+/−, n = 44; CD4⁺, Tlr9^−/− versus Tlr9^P915H/P915H p = 0.0047, Tlr9^P915H/P915H versus Tlr9^+/− p = 0.0131; CD8⁺, Tlr9^−/− versus Tlr9^P915H/P915H p = 0.0001, Tlr9^P915H/P915H versus Tlr9^+/− p = 0.0005). k-l, Percent naïve (CD62L^hi CD44^lo), activated (CD62L^hi CD44^hi) and memory (CD62L^lo CD44^hi) of CD4 and CD8 splenocytes (Tlr9^−/−, n = 36; Tlr9^P915H/P915H, n = 52; Tlr9^+/−, n = 44, (k) naïve Tlr9^−/− versus Tlr9^P915H/P915H p < 0.0001, Tlr9^P915H/P915H versus Tlr9^+/− p = 0.0018; activated Tlr9^−/− versus Tlr9^P915H/P915H p = 0.0345; (l) activated Tlr9^−/− versus Tlr9^P915H/P915H p = 0.0324, Tlr9^P915H/P915H versus Tlr9^+/− p = 0.0034; memory Tlr9^−/− versus Tlr9^P915H/P915H p = 0.0013, Tlr9^P915H/P915H versus Tlr9^+/− p = 0.0006). (a-l, For all panels, data points indicate individual mice and bars the mean ± SEM. For statistics in (a-l) * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001, one-way ANOVA with Tukey’s multiple comparisons test).

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