Proliferation/antiapoptotic markers and main genes/pathways affected by c-AID mutations in DT-AID mice. (A) Percentages of IgM⁺CD5⁺Ki67⁺ cells in the blood (left) and spleen (right) from wild-type (WT) controls (black circles), TCL1 (green circles), and DT-AID (red circles) mice determined by flow cytometry (n ≥ 10; 1-way, multiple comparison ANOVA). Arrows indicate the mouse used for the WES experiments (right panel). (B) Percentages of IgM⁺CD5⁺Bcl-2⁺ cells in the blood of wt (black circles), TCL1 (green squares), and DT-AID (red squares) mice. CD19⁺ cells from C57BL/6 mice and Jurkat T-cell line cells (ctrol +) are shown as controls. No significant differences exist (1-way, multiple comparison ANOVA; n ≥ 7). (A-B) *P < .05, **P < .001, ****P < .0001. (C) Signaling pathway analysis of the groups of genes harboring nonsynonymous c-AID mutations in DT-AID mice. The 7 pathways depicted were significantly enriched and are shown according to the number of affected genes (Panther Pathway enrichment analysis; P < .05). The 3 pathways with the highest gene counts were: “Inflammation mediated by chemokine and cytokines signaling” (IMCC; PPA: P00031), “Wnt signaling” (PPA: P00057), and “Cholecystokinin and gastrin receptors (CCKR) signaling” (PPA: P06959). (D) Mutated genes for each mouse in the 3 underlined pathways. Red asterisks identify genes previously involved in B-cell proliferative disorders.