LYMPHOMAGENESIS IN AKR.FV-1(B) CONGENIC MICE

In the AKR.Fv-1b congenic strain the Fv-1n allele of the AKR/J mice wa s substituted with the Fv-1b allele, thereby limiting viral replicatio n and spread of the endogenous N-tropic murine leukemia virus. As a re sult of this genetic change AKR.Fv-1b mice develop a low spontaneous i ncidence (7%) of T-cell lymphomas and about 28% of Ly-1+ B-cell lympho mas are observed in old mice. Characteristic changes in thymus subpopu lations of AKR/J mice (related to the formation of the dual tropic min k cell focus inducing (MCF) type virus in the thymus) were not observe d in the thymus of AKR.Fv-1b mice. In contrast to the low susceptibili ty to spontaneous T-cell lymphoma development, these mice were highly sensitive to fractionated irradiation or to radiation leukemia virus ( a mixture of N- and B-tropic viruses) induced T-cell lymphoma. Potenti al lymphoma cells (that would ultimately develop into Ly-1+ B-cell lym phomas) were demonstrated in bone marrow and spleens of 16-24-month-ol d mice. Analysis of the Ly-1+ IgM+ B-cell population in spleens of 18- month-old mice revealed a significant increase in this population (35% versus 2% in young spleens). The spontaneous Ly-1+ B-cell lymphoma in cidence could be enhanced (up to 77%) by in vivo administration of ant i-CD8 monoclonal antibody or IL-4 to 18-month-old mice. Virological an alysis of T/B-cell lymphomas for class I MCF viruses indicated that Cl ass I MCF development was tightly correlated with T-lymphoma developme nt (except radiation induced tumors that showed no MCF provirus involv ement). In contrast, Ly-1+ B-cell lymphoma development was independent of Class I MCF pathogenic virus involvement.