Fig. 4: Early expression of AID in precursor B cells has no effect in lymphomagenesis.
From: Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID
a Kaplan–Meier survival graph for R26+/AID Mb-1+/cre and R26+/+ Mb-1+/cre control mice in WT and Tp53−/− backgrounds. The number of mice in each group is indicated in brackets. Median survival for R26+/AID Mb-1+/cre Tp53−/−, 22 weeks. Histopathology analysis of tumoral mice in Tp53−/− background. TL T lymphoma, BL B lymphoma. b GFP is fully expressed from the pro-B-cell stage on. GFP reporter expression in developing B cells of R26+/AID Mb-1+/cre mice (black line) and Rosa26+/+ Mb-1+/cre control mice (gray shaded) in the bone marrow and naive B cells in the spleen. Populations were defined as B220+ CD19−, pre-pro-B; B220+ CD19+ IgM-CD25− pro-B; B220+ CD19+ IgM-CD25+ pre-B; B220+ CD19+ IgM+ IgD−, immature; B220+ CD19+ IgD+ , recirculating; B220+ , spleen naive. c SHM by R26-AID. SHM in Sμ region was analyzed by NGS in naive B cells purified from R26+/AID Mb-1+/cre and Rosa26+/+ Mb-1+/cre control mice. Aicda−/− B cells were used as control for technical background. Total mutation frequency and specific mutation frequency in C or G within AID hotspots (WRC, WRCY, and AGCT) is indicated. Two mice per genotype and one Aicda−/− were analyzed. d SHM as measure of R26-AID activity in immature B-cell populations. Sorted B-cell populations from the bone marrow, purified naive, and LPS/IL4 activated B cells were used to analyze SHM in Sμ region as in c. Mutation frequency within WRCY AID hotspots is indicated. A pool of two mice per BM/naive populations and two independent mice for activated B cells were analyzed.
