Susceptibility to lymphomas and expression of C-type RNA viruses during the graft versus host reaction

The relationship between C-type RNA viruses and the development of lymphomas was examined in mice undergoing the chronic GVHR. The GVHR was induced in F₁ hybrid recipients by administration of parental spleen cells; donor strains were selected from lines that expressed abundant, few or no detectable ecotropic viruses. There was no correlation between titer of C-type RNA viruses (both ecotropic and xenotropic) and the occurrence of lymphomas. In one combination that failed to express any detectable ecotropic virus, SWR → (SWR × NZB)F₁, lymphomas occurred in relatively high incidence. The results suggested that antigen-stimulated lymphocytes, which proliferate in abundance during the GVHR, may be preferentially susceptible to malignant transformation by viruses that, in other cells, are only weakly oncogenic or even non-oncogenic. In the course of these experiments we also found that NZB mice posses a dominant gene (or genes) that determines high-grade expression of xenotropic virus in crosses with other strains that express little or no xenotropic virus.