Tpl2 loss prolongs latency and reduces the plasma cell proliferative fraction in Vκ*MYC mice. (A) Serial serum protein electrophoresis was used to detect monoclonal gammopathy in a cohort of Vκ*MYC/Tpl2^−/− mice (14 animals) and compared with Vκ*MYC/Tpl2^+/+ controls (14 animals). Prevalence of M-spikes over time (weeks) in each cohort is shown. The latency at 50% prevalence of monoclonal gammopathy in the control group is 28 weeks and in the Vκ*MYC/Tpl2^−/− group is 42 weeks. Cohort sizes were powered (power = 80%) to detect the differences seen at 32 and 40 weeks with a *P < .05. (A) The plasma cell proliferative fraction (CD138⁺/Ki67⁺ double-positive cells) was counted against total CD138⁺ cells by immunohistochemistry, as shown in panel E. Counts were performed in >30 total CD138⁺ cells from each of >5 high-power fields from 2 mice in each group (at least 150 CD138⁺ cells per mouse). P values: *<.05, **<.01, ***< .001, ns, nonsignificant. (C) Calculation of the proliferative fraction of CD138⁺ cells was performed as delineated in panel B, but from 3 animals in each genotype with equivalent M-spikes (tumor-matched). P values: *<.05, **<.01, ***<.001. (D) Apoptotic rates were calculated as the rate of cleaved caspase 3⁺/CD138⁺ double-positive cells over total CD138⁺ cells in tumor-matched mice. Counts were performed in >30 total CD138⁺ cells from each of >5 high-power fields from 3 mice in each group (at least 150 CD138⁺ cells per mouse). P values: *<.05, **<.01, ***<.001. (E) Immunohistochemical analysis of the MYC expression, proliferative fraction (Ki67⁺), apoptotic fraction (cleaved caspase 3⁺) in CD138⁺ plasma cells from each genotype as shown (tumor-matched mice). Hematoxylin-eosin (H&E) staining is provided for morphological comparison.