1. Oncogene-specific T cells fail to eradicate lymphoma-initiating B cells in mice
- Author
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Christoph Loddenkemper, Thomas Sommermann, Gerald Willimsky, Christian Schon, Thomas Blankenstein, Dana Hoser, Philipp Lohneis, and Anja A. Kühl
- Subjects
0301 basic medicine ,Genetically modified mouse ,Lymphoma, B-Cell ,Antigens, Polyomavirus Transforming ,Immunology ,CD8-Positive T-Lymphocytes ,Biology ,Biochemistry ,Mice ,03 medical and health sciences ,Immune system ,Antigen ,immune system diseases ,Immunity ,hemic and lymphatic diseases ,medicine ,Animals ,Transluminal attenuation gradient ,Mice, Knockout ,B-Lymphocytes ,Immunity, Cellular ,Oncogene ,Cell Biology ,Hematology ,medicine.disease ,Lymphoma ,030104 developmental biology ,Cancer research ,CD8 - 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 × LoxP-Tag mice resulted in TAg-tolerant CD8+ T cells and development of B-cell lymphomas. In contrast, CD19-CreERT2 × 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.
- Published
- 2018
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