title: Effects of lymphocyte profile on development of EBV-induced lymphoma subtypes in humanized mice.
abstract: Epstein-Barr virus (EBV) infection causes both Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). The present study reveals that EBV-induced HL and NHL are intriguingly associated with a repopulated immune cell profile in humanized mice. Newborn immunodeficient NSG mice were engrafted with human cord blood CD34(+) hematopoietic stem cells (HSCs) for a 8- or 15-wk reconstitution period (denoted (8w)hN and (15w)hN, respectively), resulting in human B-cell and T-cell predominance in peripheral blood cells, respectively. Further, novel humanized mice were established via engraftment of hCD34(+) HSCs together with nonautologous fetal liver-derived mesenchymal stem cells (MSCs) or MSCs expressing an active notch ligand DLK1, resulting in mice skewed with human B or T cells, respectively. After EBV infection, whereas NHL developed more frequently in B-cell-predominant humanized mice, HL was seen in T-cell-predominant mice (P = 0.0013). Whereas human splenocytes from NHL-bearing mice were positive for EBV-associated NHL markers (hBCL2(+), hCD20(+), hKi67(+), hCD20(+)/EBNA1(+), and EBER(+)) but negative for HL markers (LMP1(-), EBNA2(-), and hCD30(-)), most HL-like tumors were characterized by the presence of malignant Hodgkin's Reed-Sternberg (HRS)-like cells, lacunar RS (hCD30(+), hCD15(+), IgJ(-), EBER(+)/hCD30(+), EBNA1(+)/hCD30(+), LMP(+)/EBNA2(-), hCD68(+), hBCL2(-), hCD20(-/weak,) Phospho STAT6(+)), and mummified RS cells. This study reveals that immune cell composition plays an important role in the development of EBV-induced B-cell lymphoma.
authors.affiliation: Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center and Sungkyunkwan University, Seoul 06351, Korea; Samsung Biomedical Research Institute, Seoul 06351, Korea;
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center and Sungkyunkwan University, Seoul 06351, Korea; Samsung Biomedical Research Institute, Seoul 06351, Korea;
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Joo
authors.affiliation: Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center and Sungkyunkwan University, Seoul 06351, Korea; Samsung Biomedical Research Institute, Seoul 06351, Korea;
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Song
authors.affiliation: Samsung Biomedical Research Institute, Seoul 06351, Korea; Department of Transplantation Surgery, Samsung Medical Center and Sungkyunkwan University School of Medicine, Seoul 06351, Korea;
authors.forename: Bongkum
authors.initials: B
authors.lastname: Choi
authors.affiliation: Samsung Biomedical Research Institute, Seoul 06351, Korea; Department of Transplantation Surgery, Samsung Medical Center and Sungkyunkwan University School of Medicine, Seoul 06351, Korea;
authors.forename: Miyoung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center and Sungkyunkwan University, Seoul 06351, Korea; Samsung Biomedical Research Institute, Seoul 06351, Korea; Department of Pathology, Samsung Medical Center and Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Seok-Hyung
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center and Sungkyunkwan University, Seoul 06351, Korea; Samsung Biomedical Research Institute, Seoul 06351, Korea; Department of Transplantation Surgery, Samsung Medical Center and Sungkyunkwan University School of Medicine, Seoul 06351, Korea; kmhyj.kim@samsung.com mkang@skku.edu.
authors.forename: Sung Joo
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center and Sungkyunkwan University, Seoul 06351, Korea; Samsung Biomedical Research Institute, Seoul 06351, Korea; kmhyj.kim@samsung.com mkang@skku.edu.
authors.forename: Myung-Soo
authors.initials: MS
authors.lastname: Kang
mesh_terms: D000818:Animals; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D008214:Lymphocytes / Q000145:classification*; D016393:Lymphoma, B-Cell / Q000145:classification / Q000276:immunology* / Q000821:virology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID
keywords: Epstein–Barr virus; Hodgkin's lymphoma; Non-Hodgkin's lymphoma; Reed–Sternberg cell; humanized mice