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

Authors

  • D. Hoser
  • C. Schön
  • C. Loddenkemper
  • P. Lohneis
  • A.A. Kühl
  • T. Sommermann
  • T. Blankenstein
  • G. Willimsky

Journal

  • Blood

Citation

  • Blood

Abstract

  • 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.


DOI

doi:10.1182/blood-2018-02-834036