Bovine leukaemia 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 (persistent lymphocytosis) and the development of a B cell leukaemia/lymphosarcoma syndrome. To gain insight into the mechanisms of BLV-induced lymphocytosis, we tested B cell survival capacity and cycling activity in peripheral blood mononuclear cells (PBMCs) from lymphocytotic, asymptomatic and control sheep. Interestingly, B cells from lymphocytotic sheep presented a lower level of spontaneous apoptosis (29%) in ex vivo cultures compared to that obtained with infected asymptomatic (42%) and control (57%/o) sheep PBMCs. Virus capsid (CA) synthesis was mainly found among surviving B cells and the percentage of CA-producing B cells correlated with the extent of B cell survival, indicating that BLV replication in B lymphocytes may promote protection from cell death. B cell survival was not linked with increases in expression of Bcl-2 mRNA or membrane leukosialin (CD43), although both are documented to be involved in some aspects of the B cell life-span. Finally, cell cycle analyses in freshly isolated PBMCs from lymphocytotic sheep revealed a slightly increased proportion of B cells in S phase compared to controls. Altogether, these data suggest that both BLV-induced B cell proliferation and extended survival are involved in the lymphocytotic stage encountered in BLV infection in sheep.
Schwartz-Cornil
I
I
URA INRA d'Immuno Pathologie Cellulaire et Moléculaire, Maisons-Alfort, France. schwartz@jouy.inra.fr
Chevallier
N
N
Belloc
C
C
Le Rhun
D
D
Lainé
V
V
Berthelemy
M
M
Mateo
A
A
Levy
D
D
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D002417:Cattle; D002453:Cell Cycle; D002470:Cell Survival; D002478:Cells, Cultured; D016583:Enzootic Bovine Leukosis / Q000276:immunology* / Q000503:physiopathology; D005434:Flow Cytometry; D015368:Human T-lymphotropic virus 1; D006801:Humans; D001909:Leukemia Virus, Bovine; D008218:Lymphocytosis / Q000276:immunology* / Q000821:virology; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger; D012016:Reference Values; D012756:Sheep; D014158:Transcription, Genetic
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger