Oncogene-specific T cells fail to eradicate lymphoma-initiating B cells in mice

To date, little is known about the interaction between (pre-)malignant B cells and T cells. We generated transgenic mice that allow B cell-specific induction of the oncogene SV40 large T-antigen (TAg) to analyze the role of oncogene-specific T cells during sporadic B cell lymphoma development. Constitutive TAg expression in CD19-Cre x LoxP Tag mice resulted in TAg-tolerant CD8(+) T cells and development of B cell lymphomas. In contrast, CD19 CreER(T2) x LoxP Tag mice retained TAg-competent CD8(+) T cells at time of oncogene induction and TAg expression in few B cells of adult mice resulted in exceptionally rare lymphoma formation late in life. Increased lymphoma incidence in the absence of TAg-specific T cells suggested T cell-mediated inhibition of lymphoma progression. However, TAg-initiated B cells were not eliminated by T cells and detected long-term. Our results demonstrate a failure of the immune system to eradicate lymphoma-initiating B cells, retaining the risk of lymphoma development.