Sequential changes of T- and B-cells, virus antigen expression and primary histologic tumor diagnosis in virus-induced lymphomagenesis of mice.

T- and B-cell counts, estimation of Ig receptor fluidity, and expression of virus-coded antigens were correlated with histological findings during the development of virus-induced mouse lymphoma. Tested were BALB/c mice after infection with the strongly oncogenic Moloney leukemia virus (MLV), the moderately oncogenic (in BALB/c mice) Gross passage A virus (GLV-A), and the essentially non-oncogenic Gross 3T3 tissue culture virus (GLV-T). Methods included immunofluorescence microscopy with antisera against T-cells, B-cells and MLV intact virus, routine histology, and electron microscopy. Following time sequence of changes was observed in mice with oncogenic MLV- and GLV-A infection but not in GLV-T infection: Significant decrease of Ig receptor fluidity and expression of virus antigen were observed already at the initial investigation, i.e. 2 weeks post virus infection. This was followed by significant decreases in percent T-cells 5--8 weeks later, accompanied by histologic atrophy of the thymus and of thymus-dependent regions of lymphatic tissues. Another 2--8 weeks after the decrease in percent T-cells occurred, the first lymphomatous foci became obvious in the thymus. Clinically overt and generalized lymphoma was diagnosed at 20--30 weeks post virus infection. Ultrastructurally, some changes in the arrangement and quantity of cytoplasmic microfilaments were noted in proliferating lymphoblasts and in lymphoma cells. It is concluded, that the described changes were related to the oncogenic potential of mouse C-type RNA viruses and not just to virus infection per se.