Abstract
BackgroundEpstein-Barr virus (EBV) has a close association with various types of human lymphomas. Animal models are essential to elucidate the pathogenesis of human EBV-associated lymphomas. The aim of the present study is to evaluate the association between human IgG concentration and EBV-associated lymphoma development in huPBL/SCID mice.MethodsHuman peripheral blood lymphocytes (hu-PBL) from EBV-seropositive donors were inoculated intraperitoneally into SCID mouse. Immunohistochemical staining was used to examine differentiated antigens of tumor cells. EBV infection of the induced tumors was detected by in situ hybridization. IgG concentrations in the serums of 12 SCID mice were measured by unidirectional immunodiffusion assay.Results21 out of 29 mice developed tumors in their body. Immunohistochemical staining showed that all induced tumors were LCA (leukocyte common antigen) positive, B-cell markers (CD20, CD79a) positive, and T-cell markers (both CD3 and CD45RO) negative. The tumors can be diagnosed as human B-cell lymphomas by these morphological and immunohistochemical features. In situ hybridization exhibited resultant tumor cells had EBV encoded small RNA-1 (EBER-1). Human-derived IgG could be found in the serum from SCID mice on the 15th day following hu-PBL transplantation, and IgG levels increased with the tumor development in 6 hu-PBL/SCID chimeras.ConclusionsIntraperitoneal transfer of hu-PBLs from EBV+ donors to SCID mice leads to high human IgG levels in mouse serum and B cell lymphomas. Our findings suggest that increasing levels of human-derived IgG in peripheral blood from hu-PBL/SCID mice could be used to monitor EBV-related human B-cell lymphoma development in experimental animals.
Highlights
Epstein-Barr virus (EBV) has a close association with various types of human lymphomas
Epstein-Barr virus (EBV) is a ubiquitous human herpes virus that persists in most human bodies as a lifelong latent infection in host lymphocytes after a primary viral encounter, and it has been confirmed to be the etiological factor of infectious mononucleosis [1,2]
Hu-PBLs from EBV-seropositive donors were inoculated intraperitoneally into 29 Severe combined immunodeficient (SCID) mice by 1 × 108 PBLs resuspended in 1 ml RPMI1640 medium per mouse, such mice are hereafter referred to as hu/SCID chimeras
Summary
Epstein-Barr virus (EBV) has a close association with various types of human lymphomas. Animal models are essential to elucidate the pathogenesis of human EBV-associated lymphomas. Because SCID mice lack functional T or B lymphocytes, they can be engrafted with functioning human hematolymphoid cells to create human/SCID chimeras [7,8] In immunosuppressed individuals, such as post-transplant patients, the presence of EBV-infected B cells may lead to lymphoproliferative disease [9]. Injection of human peripheral blood lymphocytes (huPBLs) or hematopoietic stem cells from EBV-positive donors into SCID mice induces human lymphoproliferative disease in the humanized SCID recipients [10,11]. This xenochimeric human-mouse model can be used to elucidate the mechanisms of EBV-specific lymphomagenesis and to assess novel therapeutic approaches. The aim of the present study is to detect molecular biomarkers of the EBV-induced lymphomas in hu-PBL/SCID mice and to measure serum IgG levels in hu-PBL/SCID chimeras
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