title: Identification of IgH gene rearrangement and immunophenotype in an animal model of Epstein-Barr virus-associated lymphomas.
abstract: Epstein-Barr virus (EBV) is a human oncogenic herpesvirus associated with lymphoma and nasopharyngeal carcinoma. Because the susceptible hosts of EB virus are limited to human and cotton-top tamarins (Saguinus oedipus), there have been no appropriate animal models until the lymphoma model induced by EBV in human peripheral blood lymphocyte (hu-PBL)/SCID chimeric mice was reported. However, it is still controversial whether the EBV-associated lymphoma induced in hu-PBL/SCID mice is a monoclonal tumor. In this study, we transplanted normal human peripheral blood lymphocytes (hu-PBL) from six donors infected with EBV into SCID mice to construct hu-PBL/SCID chimeric mice. The induced tumors were found in the mediastinum or abdominal cavity of SCID mice. Microscopic observation exhibited tumor cells that were large and had a plasmablastic, centroblastic or immunoblastic-like appearance. Immunophenotyping assays showed the induced tumors were LCA-positive, CD20/CD79a-positive (markers of B cells), and CD3/CD45RO-negative (markers of T cells). A human-specific Alu sequence could be amplified by Alu-PCR. This confirmed that induced tumors were B-cell lymphomas originating from the transplanted human lymphocytes rather than mouse cells. EBER in situ hybridization detected positive signals in the nuclei of the tumor cells. Expression of EBV-encoded LMP1, EBNA-1, and EBNA-2 in the tumors was significantly positive. PCR-based capillary electrophoresis analysis of IgH gene rearrangement revealed a monoclonal peak and single amplification product in all six cases of induced tumors. This indicated that EBV can induce monoclonal proliferation of human B lymphocytes and promotes the development of lymphoma. J. Med. Virol. 88:1804-1813, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Cancer Research Institute, College of Medicine, University of South China, Chang Sheng Xi Avenue 28, Hengyang, Hunan 421001, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cancer Research Institute, College of Medicine, University of South China, Chang Sheng Xi Avenue 28, Hengyang, Hunan 421001, P.R. China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Peng
authors.affiliation: Cancer Research Institute, College of Medicine, University of South China, Chang Sheng Xi Avenue 28, Hengyang, Hunan 421001, P.R. China.
authors.forename: Yunlian
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Cancer Research Institute, College of Medicine, University of South China, Chang Sheng Xi Avenue 28, Hengyang, Hunan 421001, P.R. China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Gan
authors.affiliation: Cancer Research Institute, College of Medicine, University of South China, Chang Sheng Xi Avenue 28, Hengyang, Hunan 421001, P.R. China.
authors.forename: Chengkun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Shanghai Center for Bioinformation Technology (SCBIT), Shanghai Academy of Science and Technology, Shanghai 201203, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xie
authors.affiliation: Cancer Research Institute, College of Medicine, University of South China, Chang Sheng Xi Avenue 28, Hengyang, Hunan 421001, P.R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Xie
authors.affiliation: Cancer Research Institute, College of Medicine, University of South China, Chang Sheng Xi Avenue 28, Hengyang, Hunan 421001, P.R. China.
authors.forename: Runliang
authors.initials: R
authors.lastname: Gan
authors.affiliation: Hunan Provincial Key Laboratory for Special Pathogen Prevention and Control, University of South China, Hunan 421001, P.R. China.
authors.forename: Yimou
authors.initials: Y
authors.lastname: Wu
mesh_terms: D020087:Alu Elements; D000818:Animals; D004195:Disease Models, Animal; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D015321:Gene Rearrangement; D004854:Herpesvirus 4, Human; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016130:Immunophenotyping; D017403:In Situ Hybridization; D017710:Lymphocyte Transfusion; D016393:Lymphoma, B-Cell / Q000821:virology*; D016513:Mice, SCID; D014763:Viral Matrix Proteins / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
chemical_list: C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D007143:Immunoglobulin Heavy Chains; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C417029:EBV-encoded nuclear antigen 1
keywords: EBV-associated lymphoma; Epstein-Barr virus (EBV); SCID mouse; gene rearrangement; immunophenotype