title: 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 IgM(high) B-cells were increased in blood lymphocytes from BLV-infected cattle. IgM(high) B-cells mainly expressed BLV antigens, whereas IgM(low) 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 IgM(low) B-cells than those in IgM(high) B-cells. Moreover, lymphoma cells obtained from the lymph nodes of 14 BLV-infected cattle contained IgM(low) or IgM(-) B-cells but no IgM(high) B-cells. To our knowledge, this is the first study to demonstrate that IgM(high) B-cells mainly comprise BLV-expressing cells, whereas IgM(low) B-cells comprise a high proportion of BLV-silencing B-cells in BLV-infected cattle.
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Ryoyo
authors.initials: R
authors.lastname: Ikebuchi
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Konnai
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Okagawa
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Asami
authors.initials: A
authors.lastname: Nishimori
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Nakahara
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Murata
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000821:virology*; D002417:Cattle; D016583:Enzootic Bovine Leukosis / Q000276:immunology* / Q000821:virology*; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions; D001909:Leukemia Virus, Bovine / Q000235:genetics*; D046228:Microarray Analysis; D011533:Proviruses / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000096:biosynthesis*
chemical_list: D000956:Antigens, Viral; D014764:Viral Proteins