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

• Published in: Blood 2018-08, Vol.132 (9), p.924-934
• Main Authors: Hoser, Dana, Schön, Christian, Loddenkemper, Christoph, Lohneis, Philipp, Kühl, Anja A., Sommermann, Thomas, Blankenstein, Thomas, Willimsky, Gerald
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Polyomavirus Transforming - genetics; Antigens, Polyomavirus Transforming - immunology; B-Lymphocytes - immunology; B-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Immunity, Cellular; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - immunology; Lymphoma, B-Cell - pathology; Mice; Mice, Knockout
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-02-834036

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. •Absence of oncogene-specific T cells leads to increased B-cell lymphoma incidence in a new mouse model.•Premalignant lymphoma-initiating B cells are not eradicated by the immune system, retaining the risk of lymphoma development. [Display omitted]