Panel A: A schematic diagram shows generation of eukaryotic translation initiation factor 3 subunit E conditional-knockout mice with yellow fluorescent protein reporter expression. Panel B: A Kaplan–Meier survival curve compares survival among Cγ1Cre, eukaryotic translation initiation factor 3 subunit E floxed, and conditional-knockout mice. The x-axis represents age in months, and the y-axis represents percentage survival. Panel C: Photographs compare spleen, mesenteric lymph nodes, lung, kidney, and liver morphology between control and conditional-knockout mice, demonstrating splenomegaly, lymphadenopathy, and tumor infiltration. Panel D: Pie charts visualize distributions of the three most enriched clonotypes across seven conditional-knockout tumor samples, showing clone frequencies and cell numbers. Panel E: Hematoxylin and eosin-stained histological images show low-power and high-power microscopic views of tumors arising in conditional-knockout mice. Panel F: Experimental schematic illustrates tumor transplantation into recombination activating gene 2-knockout recipient mice, alongside secondary-tumor photographs and stacked bar-plot summaries. Panel G: Flow-cytometry plots analyze primary and secondary B-cell lymphoma populations in conditional-knockout and recombination activating gene 2-knockout recipient mice. Panel H: Scatter plots quantify percentages of yellow fluorescent protein-positive cells within primary and secondary tumor populations. Panel I: Immunoblot images compare eukaryotic translation initiation factor 3 subunit E protein expression in purified cluster of differentiation 4-positive T cells and B cells from tumors and wild-type controls.
Mice with B cell–specific deletion of Eif3e develop lymphoma. (A) Schematic depiction of Eif3e-conditional knockout mice with YFP reporter (Eif3efl/flCγ1CreRosa26-YFPLSL, termed cKO). (B) Kaplan–Meier survival curves of Cγ1Cre (orange, n = 6), Eif3efl (black, n = 32), and cKO (red, n = 25) mice. **P < 0.01; ****P < 0.0001. Statistical significance is calculated using the log-rank test. (C) Splenomegaly, lymphadenopathy, and tumor cell infiltration (arrows) into the lung, kidney, and liver of 10- to 13-mo-old cKO mice. Scale bar, 1 cm. (D) Pie chart visualizing the distribution of the top three most enriched clonotypes in seven cKO mice. Six samples were primary tumors from mouse #29 (lung), #30 (liver), #31 (spleen), #32 (spleen), #33 (thymus), and #34 (lung and thymus). One sample was secondary tumor transplanted from primary nodule of mouse #27 (liver). Both the number of cells and clones are displayed. (E) Representative H&E staining of tumors in cKO mice. Top panels, low-power views (black scale bars, 1 mm). Bottom panels, high-power views (blue scale bars, 20 μm). (F) Tumor transplantation into Rag2−/− mice. Upper panel, experimental outline. Lower left, representative photos of secondary tumors in recipient mice. Lower right, stacked bar plot summarizing the types of secondary tumors. Scale bar, 1 cm. (G) Flow cytometry analysis of primary and secondary B cell lymphoma in cKO and Rag2−/− recipient mice, respectively. (H) Percentages of YFP+ cells in primary and secondary tumors. (I) Immunoblot analysis of eIF3e expression in purified CD4+ T and B cells from tumors in cKO mice. Controls were CD4+ T (upper panel) and B cells (lower panel) purified from the splenocytes of wild-type mice. H&E, hematoxylin and eosin. Source data are available for this figure: SourceData F1. The #numbers in the figure correspond to the mouse numbers in Table S1.