Transformed phenotype of enzootic bovine lymphoma reflects differentiation-linked leukemogenesis

Detailed genotypic and phenotypic characteristics of enzootic bovine lymphoma were defined to determine if tumor cell characteristics were consistent with the etiologic agent of this disease. Lymphoid tumors from cattle with serologic evidence of bovine leukemia virus (BLV) infection were examined by Southern blot analysis to confirm the presence and copy number of integrated BLV. All cases of enzootic bovine lymphoma examined contained 1 to 4 BLV proviral copies in tumor DNA and revealed immunoglobulin gene rearrangement (Ig). Tumors were further characterized immunohistochemically with a panel of 8 monoclonal antibodies to bovine lymphocyte determinants and B cell differentiation markers. The majority of cases examined expressed Ia/DR, 11 of 17 cases also expressed surface IgM, frequently with another Ig isotype. To definitively characterize the stage of B cell differentiation represented in the transformed phenotype, genotypic evidence of isotype switching was examined in these tumors. Our results demonstrated that enzootic bovine lymphomas are tumors of mature B cells with common characteristics, suggesting that pressures associated with BLV infection which favor tumor development are manifested late in B cell ontogeny, possibly during the isotype switch period.