Bovine leukemia virus induces CD5- B cell lymphoma in sheep despite temporarily increasing CD5+ B cells in asymptomatic stage.

To investigate bovine leukemia virus (BLV)-induced leukemogenesis, we infected sheep with BLV and used flow-cytometric and immunohistological analysis to characterize the phenotypic alterations in lymphocytes from peripheral blood and lymph nodes taken from the animals with lymphoma at various stages. In sheep at the asymptomatic stage, depending on the extent of progression of the disease, the proportions of CD2(+)-, CD4(+)-, CD8(+)-, and gamma delta TCR(+)-T cells that coexpressed CD5 decreased, but CD5+ sIgM+ cells as well as CD5- sIgM+ cells increased for a period. The number of CD5+ B cells, however, rapidly decreased in the lymphoma stage. On the other hand, neoplastic lymphocytes appeared to be a monoclonal population derived from a single cell with surface phenotypes of sIgM+, B-cell-specific molecule B2+, major histocompatibility complex (MHC) class II+, OvCD5-, OvCD2-, OvCD4-, OvCD8-, gamma delta TCR-, which suggests that only CD5- B cells proliferate clonally when the disease proceeds to the lymphoma stage. Thus, rapid decrease of CD5+ B cells may be used as a marker of lymphoma stage. To identify the BLV provirus in the CD5- B and CD5+ B cells throughout the course of disease, each fraction of CD5- B and CD5+ B cell was sorted from the peripheral blood by flow cytometry and nested double polymerase chain reaction was performed. In BLV-infected but healthy sheep, BLV integrated both CD5- B and CD5+ B cells. In lymphoma, however, BLV provirus was detected only in CD5- B cells but not in CD5+ B cells. Therefore it appears that a disappearance of BLV-infected CD5+ cells is one of the critical events leading to CD5- B cell lymphoma in sheep. This is in contrast to the BLV-induced lymphoma in cattle which shows CD5+ phenotype.