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

Abstract

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 γδTCR +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.