UV-Induced B-Cell Lymphomas in p53 Heterozygous Mice.

The association between ultraviolet (UV) irradiation and skin cancer induction is well known. Recently, UV exposure was associated with the induction of internal lymphoid malignancies in UV-irradiated p53 heterozygous mice. Here we characterize the non-skin cancer that develops in the lymphoid organs of UV-irradiated mice and found that UV exposure promotes the induction of a B-cell lymphoma. p53 heterozygous mice were exposed to UVB irradiation (10KJ/m^2; three times a week) supplied by a bank of FS40 sunlamps. After thirty weeks, we collected spleen cells from 5 irradiated mice, prepared single suspensions, pooled the cells and injected 2X10⁶ cells/flank (subcutaneous injection) into Rag2−/−mice. The subcutaneous tumors that developed in the Rag2−/−mice were successfully transplanted into other Rag2−/−mice and adapted to grow in vitro. Flow cytometric analysis indicated that enlarged cells were positive for CD19, B220, IgM, CD24, CD40, B7-1, B7-2, but negative for CD43, BP-1, CD127, CD3, CD4, CD8, CD49b, NK1.1, Thy1.2, Gr-1. This phenotype is compatible with a mature B cell but also express CD5, CD11b, CD117. Immunohistchemical analysis confirmed that the tumor cells were of B-cell origin and southern blot analysis demonstrated rearrangement of Immunoglobulin heavy chain. Chromosomal analysis revealed a translocations, t (14;19). Subcutaneous injection of the tumor cells into Rag2−/− mice resulted in an aggressive tumor that infiltrated into the lymph nodes, the spleen and the bone marrow. After establishing the cell line from this B-cell lymphoma, we transfected GFP by using lentiviral vector to mark and injected into Rag2−/− mice. First, the cells bearing GFP infiltrated into the lymph nodes, and then into the spleen and the bone marrow. We also found that this cell line produced IL-10, which can promote lymphoma growth and can cause systemic immunosuppression (