Ex vivo survival of peripheral blood mononuclear cells in sheep induced by bovine leukemia virus (BLV) mainly occurs in CD5- B cells that express BLV.
Bovine leukemia virus (BLV) is the etiologic agent of enzootic bovine leukosis (EBL). In a previous report, we found that in a sheep model, only CD5(-) B cells proliferated clonally, while CD5(+) B cells rapidly decreased when the disease progressed to the lymphoma stage. We demonstrate here that, although both CD5(+) and CD5(-) B cells, but not CD4(+) T, CD8(+) T and gammadeltaTCR(+)T cells, are protected from spontaneous ex vivo apoptosis in sheep infected with wild-type and a mutant BLV that encodes a mutant Tax D247G protein with elevated trans-activation activity, only CD5(-) B cells become the main target for ex vivo survival when the disease proceeds to the persistent lymphocytotic stage, which showed an increased expansion of the CD5(-) B cells. In addition, we identified, by four-color flow cytometric analysis, that in CD5(-) B cells, the apoptotic rates of cells that expressed wild-type and mutant BLV were greatly decreased compared with those of BLV-negative cells. There was only a slight reduction in the apoptotic rates in BLV-positive cells from CD5(+) B cells. In addition, supernatants from peripheral blood mononuclear cell (PBMC) cultures from wild-type- and mutant BLV-infected sheep mainly protected CD5(-) B cells from spontaneous apoptosis. Our results suggest that, although BLV can protect both CD5(+) and CD5(-) B cells from ex vivo apoptosis, the mechanisms accounting for the ex vivo survival between these two B-cell subsets differ. Therefore, it appears that the phenotypic changes in cells that express CD5 at the lymphoma stage could result from a difference in susceptibility to apoptosis in CD5(+) and CD5(-) B cells in BLV-infected sheep.
Takahashi
Masahiko
M
Retrovirus Research Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Tajima
Shigeru
S
Takeshima
Shin-Nosuke
SN
Konnai
Satoru
S
Yin
Shan Ai
SA
Okada
Kosuke
K
Davis
William C
WC
Aida
Yoko
Y
D000818:Animals; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000502:physiology* / Q000821:virology*; D015704:CD4 Antigens / Q000032:analysis; D018956:CD5 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis; D002417:Cattle; D002478:Cells, Cultured; D006800:Deltaretrovirus Infections / Q000503:physiopathology / Q000821:virology*; D018450:Disease Progression; D016583:Enzootic Bovine Leukosis / Q000821:virology; D005434:Flow Cytometry; D016355:Genes, pX; D001909:Leukemia Virus, Bovine / Q000235:genetics / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000502:physiology / Q000821:virology; D020125:Mutation, Missense; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D012756:Sheep
D015704:CD4 Antigens; D018956:CD5 Antigens; D016827:CD8 Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta