BOVINE LEUKEMIA VIRUS-INDUCED LYMPHOCYTOSIS IN SHEEP IS ASSOCIATED WITH REDUCTION OF SPONTANEOUS B-CELL APOPTOSIS

Experimental inoculation of sheep with bovine leukaemia virus (BLV), a retrovirus homologous to the human T-lymphotropic virus type 1 (HTLV- 1), induces a chronic expansion of the B lymphocyte population (persis tent lymphocytosis) and the development of a B cell leukaemia/lymphosa rcoma syndrome, To gain insight into the mechanisms of BLV-induced lym phocytosis, we tested B cell survival capacity and cycling activity in peripheral blood mononuclear cells (PBMCs) from lymphocytotic, asympt omatic and control sheep, Interestingly, B cells from lymphocytotic sh eep presented a lower level of spontaneous apoptosis (29%) in ex vivo cultures compared to that obtained with infected asymptomatic (42%) an d control (57%) sheep PBMCs, Virus capsid (CA) synthesis was mainly fo und among surviving B cells and the percentage of CA-producing B cells correlated with the extent of B cell survival, indicating that BLV re plication in B lymphocytes may promote protection from cell death, B c ell survival was not linked with increases in expression of Bcl-2 mRNA or membrane leukosialin (CD43), although both are documented to be in volved in some aspects of the B cell life-span, Finally, cell cycle an alyses in freshly isolated PBMCs from lymphocytotic sheep revealed a s lightly increased proportion of B cells in S phase compared to control s. Altogether, these data suggest that both BLV-induced B cell prolife ration and extended survival are involved in the lymphocytotic stage e ncountered in BLV infection in sheep.