Kinase activity of Syk is important for BCR hyper-responsiveness in cGVHD B cells ex vivo. B cells isolated from patients without cGVHD (n = 4, open circles) and with cGVHD (n = 4, filled squares) stained with CFSE, treated with R406 (0, 0.01, and 0.1 μM) as indicated, and stimulated with (A-B) α-IgM (50 μg/mL) or (C-D) α-CD40 (100 ng/mL) + IL-4 (5 ng/mL) for 6 days. (A) Frequency of proliferation in response to α-IgM in B cells from patients (left) without cGVHD (open circles) and (right) with cGVHD (filled squares). (Left) ANOVA, P < .0001; *P < .05. (Right) ANOVA, P < .0067; *P < .05. (B) Percent change in number of B cells from A: [Percent change = (V2 – V1)/V1 × 100]. ANOVA, P = .0002; *P < .05. (C) Frequency of proliferation in response to α-CD40 + IL-4 in B cells from patients (left) without cGVHD (open circles) and (right) with cGVHD (filled squares). (D) Percent change in number of B cells from C: [Percent change = (V2 – V1)/V1 × 100]. Data are median ± range pooled from 3 independent experiments.