Reduced IL-6, vascular endothelial growth factor (VEGF), and IL-1ra production by B cells upon toll-like receptor 9 (TLR9) stimulation in active systemic lupus erythematosus (SLE) patients compared to healthy donors (HD). (A) To compare the production of cytokines (group 1 and 2) upon TLR9 stimulation by healthy donors with SLE patients, the SLE cohort was divided in two groups with low disease activity (SLEDAI <6, n = 6) and high disease activity (SLEDAI ≥6, n = 12). IL-6, VEGF, and IL-1ra produced by B cells upon TLR9 stimulation were significantly reduced in SLE with high SLEDAI compared to healthy donors (one way analysis of variance with Dunnett’s post hoc test, *P <0.05). (B) Representative flow cytometry analysis plots showing IL-10-producing B cells after 2 days of peripheral blood mononuclear cells (PBMC) culture without (left) or with (right) CpG stimulation. Combined data from 6 SLE patients and 10 healthy controls for the frequency of IL-10-producing B cells (left graph) and the overall production of IL-10 by B cells (right graph, MFI = mean fluorescence intensity, reflecting amount per cell) (Mann-Whitney U-test and Wilcoxon test; ns: not significant, *P <0.05, **P <0.01).