CD48^−/− mice develop lymphoma with age. (A) A cohort of CD48^−/− (n = 10) and WT mice were followed and monitored closely until 65 weeks of age or until morbidity was observed. The spleen, thymus, and sternum were then collected for pathology. None of the WT mice hade visible tumors in these organs, however, 90% of the CD48-null mice developed lymphoma (log-rank [Mantel-Cox] test, P = .0003). (B) Flow cytometry was performed on spleens collected from WT and CD48^−/− mice. The tumors in the CD48^−/− mice appeared to be CD19^dim, CD44⁺, Thy1.2⁻ and a large portion of these cells were positive for early B-cell lineage. (C) An example of H&E staining of thymus and spleen from WT and CD48 mice. Large malignant lymphomas can be seen in both organs in the majority of the CD48-null mice, and the lymphomas had characteristics of follicular lymphoma. (D) Mean fluorescence intensity pPAK and pERk for CD19^dim cells was collected and a significant increase in the activation of the PAK/Erk pathway was seen in the CD48-null tumor cells (2-way ANOVA, *P < .05). (E) Mean fluorescence intensity pPAK and pERk for early B-cell Ag⁺ cells was collected and a significant increase in the activation of the PAK/Erk pathway was seen in the CD48-null tumor cells (2-way ANOVA, *P < .05).