SOX11 expression promotes BCR signaling in MCL cells. (A) p-BTK-Y223 and p-PLCγ-Y759 levels in CD5⁺CD19⁺CD23⁻ (B1a) splenocytes from Tg-SOX11 mice as compared with WT controls. (B) Elevated response to anti-IgM stimulation of BCR signaling seen by increased p-BTK(Y223) and p-PLCγ(Y759) levels in Tg-SOX11-B1a splenocytes as compared with WT-B1a splenocytes assayed by flow cytometry. (C) SPADE analysis (upper panel) showing increased p-CREB levels in various B-cell subsets of Tg-SOX11 and WT splenocytes in anti-IgM–stimulated B cells. The heat map (lower panel) summarizes findings for all the key members of the BCR signaling pathway showing elevated expression of p-BTK, p-PLCγ2, p-ERK, p-p38, p-MAPKAP2, and p-CREB across B-cell subsets in Tg-SOX11 overexpressing and WT splenocytes in response to IgM stimulation. (D) Treatment of fluorescence-activated cell–sorted SOX11-overexpressing CD5⁺CD19⁺ splenocytes with 100 nM of ibrutinib (Ibru) prior to anti-IgM stimulation showing reversibility of elevated BCR signaling. Ctrl, control.