The monoallelic loss of S1pr2 promotes hyperproliferation of the GC B-cell compartment and increases the lymphoma burden in a spontaneous and a serial transplantation model of MYC-driven lymphomagenesis. (A-F) S1pr2^+/+ and S1pr2^+/− mice on the BL/6 background were immunized twice intraperitoneally with 200 μL 10% SRBC, with a 10-day interval between the 2 immunizations. (A-C) Mice were euthanized 10 days after the last immunization and GC B cells were flow cytometrically identified as CD95^hi CD38^lo in the CD19⁺ B-cell compartment. GC B-cell frequencies in % of all CD19⁺ B cells as well as absolute numbers per spleen are shown alongside representative FACS plots. Nonimmunized littermates are shown as control. (D-F) The GC area (arbitrary units) of immunized mice was determined by quantifying 3 Ki-67-stained spleen sections per mouse (D) using ImageJ. (E-F) Representative pictures of spleens of immunized S1pr2^+/+ and S1pr2^+/− mice are shown. Size bar represents 1000 μm; arrows point to GCs. (A-B,D) Every dot represents 1 mouse and data from 5 pooled experiments are shown. (G-H) One million lymph node cells per mouse, harvested from 3 S1pr2^+/+ and 3 S1pr2^+/−MYC^tg donor mice of the cohorts shown in supplemental Figure 2F were injected IV into wild-type BL/6 recipients. Mice were palpated every other day for enlarged lymph nodes and euthanized after 20 days (ie, when the first mice showed disease symptoms). (G) Spleen and (H) lymph node weights were determined. Lymph node weights represent the average of 2 inguinal and 2 axillary lymph nodes. Control mice were not injected with tumor cells. (A-B,D,G-H) Horizontal lines indicate medians; P values were calculated using the Mann-Whitney U test. *P < .05; **P < .01.