Differences in cellular function and viral protein expression between IgMhigh and IgMlow B-cells in bovine leukemia virus-infected cattle

Abstract

Bovine leukemia virus (BLV) induces abnormal B-cell proliferation and B-cell lymphoma in cattle, where the BLV provirus is integrated into the host genome. BLV-infected B-cells rarely express viral proteins in vivo, but short-term cultivation augments BLV expression in some, but not all, BLV-infected B-cells. This observation suggests that two subsets, i.e. BLV-silencing cells and BLV-expressing cells, are present among BLV-infected B-cells, although the mechanisms of viral expression have not been determined. In this study, we examined B-cell markers and viral antigen expression in B-cells from BLV-infected cattle to identify markers that may discriminate BLV-expressing cells from BLV-silencing cells. The proportions of IgMhigh B-cells were increased in blood lymphocytes from BLV-infected cattle. IgMhigh B-cells mainly expressed BLV antigens, whereas IgMlow B-cells did not, although the provirus load was equivalent in both subsets. Several parameters were investigated in these two subsets to characterize their cellular behaviour. Real-time PCR and microarray analyses detected higher expression levels of some proto-oncogenes (e.g. Maf, Jun and Fos) in IgMlow B-cells than those in IgMhigh B-cells. Moreover, lymphoma cells obtained from the lymph nodes of 14 BLV-infected cattle contained IgMlow or IgM− B-cells but no IgMhigh B-cells. To our knowledge, this is the first study to demonstrate that IgMhigh B-cells mainly comprise BLV-expressing cells, whereas IgMlow B-cells comprise a high proportion of BLV-silencing B-cells in BLV-infected cattle.