BOVINE LEUKEMIA-VIRUS INDUCES CD5- B-CELL LYMPHOMA IN SHEEP DESPITE TEMPORARILY INCREASING CD5-CELLS IN ASYMPTOMATIC STAGE( B)

To investigate bovine leukemia virus (BLV)-induced leukemogenesis, we infected sheep with BLV and used flow-cytometric and immunohistologica l analysis to characterize the phenotypic alterations in lymphocytes f rom peripheral blood and lymph nodes taken from the animals with lymph oma at various stages. In sheep at the asymptomatic stage, depending o n the extent of progression of the disease, the proportions of CD2(+)- , CD4(+)-, CD8(+)-, and gamma delta TCR(+)-T cells that coexpressed CD 5 decreased, but CD5(+)sIgM(+) cells as well as CD5(-)sIgM(+) cells in creased for a period, The number of CD5(+) B cells, however, rapidly d ecreased in the lymphoma stage. On the other hand, neoplastic lymphocy tes appeared to be a monoclonal population derived from a single cell with surface phenotypes of sIgM(+), B-cell-specific molecule B2(+), ma jor histocompatibility complex (MHC) class II+, OvCD5(-), OvCD2(-), Ov CD4(-), 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(-) a and C D5(+) a cells throughout the course of disease, each fraction of CD5(- ) B and CD5(+) B cell was sorted from the peripheral blood by flow cyt ometry and nested double polymerase chain reaction was performed. In B LV-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 disa ppearance of BLV-infected CD5(+) cells is one of the critical events l eading to CD5(-) B cell lymphoma in sheep. This is in contrast to the BLV-induced lymphoma in cattle which shows CD5(+) phenotype. (C) 1994 Academic Press, Inc.