Characterization of a novel mouse model for human B-cell lymphomas (127.31)

Abstract

Abstract The risk of developing lymphoma is markedly increased after solid organ transplantation. Up to 20% of people who receive a solid organ transplant develop a lymphoma. Calcineurin (CN) A beta knockout (Cnab-/-) mice do not reject allogeneic tumors suggesting an immunosuppressive state, is also a unique model for reverse immunosurveillance. Currently, there is no mouse model for low grade lymphomas based on immune dysregulation. Since we observed a spontaneous activation of T cells, and B-cell lymphomas in CNAβ deficient mice, we hypothesize that CN is involved in T-cell regulation, the lack of regulation causes smoldering inflammation which in turn activates B cells and results in lymphomagenesis. The lymphomas in Cnab-/- mice are positive for B cell surface marker (CD21) but negative for T cell (TCRβ) markers and they are clonal in origin and exhibit malignant (destroying the normal architecture of adjoining area) phenotype. In addition, we do see spontaneous activation of T cells in Cnab-/- mice early in life and continue to accumulate, and B cells later when they are old with mild inflammatory lesions in the gut and liver in Helicobacter-free (clean) colony. Since inflammation is considered to be one of the hallmarks of cancer and also the root cause of cancer, this is a novel mouse model for understanding a slow growing, difficult to cure form of lymphomas.