title: Tonsillar CD56brightNKG2A+ NK cells restrict primary Epstein-Barr virus infection in B cells via IFN-γ.
abstract: Natural killer (NK) cells constitute the first line of defense against viruses and cancers cells. Epstein-Barr virus (EBV) was the first human virus to be directly implicated in carcinogenesis, and EBV infection is associated with a broad spectrum of B cell lymphomas. How NK cells restrict EBV-associated oncogenesis is not understood. Here, we investigated the efficacies and mechanisms of distinct NK cell subsets from tonsils, the portal of entry of EBV, in limiting EBV infection in naïve, germinal center-associated and memory B cells. We found that CD56bright and NKG2A expression sufficiently characterizes the potent anti-EBV capacity of tonsillar NK cells. We observed restriction of EBV infection in B cells as early as 18 hours after infection. The restriction was most efficient in naïve B cells and germinal center-associated B cells, the B cell subsets that exhibited highest susceptibility to EBV infection in vitro. IFN-γ release by and partially NKp44 engagement of CD56bright and NKG2A positive NK cells mediated the restriction that eventually inhibited B-cell transformation. Thus, harnessing CD56brightNKG2A+ NK cell function might be promising to improve treatment strategies that target EBV-associated B cell lymphomas.
authors.affiliation: Children's Research Center, University Children's Hospital, Experimental Infectious Diseases and Cancer Research, Zurich, Switzerland.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Jud
authors.affiliation: Children's Research Center, University Children's Hospital, Experimental Infectious Diseases and Cancer Research, Zurich, Switzerland.
authors.forename: Monika
authors.initials: M
authors.lastname: Kotur
authors.affiliation: Children's Research Center, University Children's Hospital, Experimental Infectious Diseases and Cancer Research, Zurich, Switzerland.|Division of Infectious Diseases, and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Berger
authors.affiliation: Children's Research Center, University Children's Hospital, ENT Clinic, Zurich, Switzerland.
authors.forename: Claudine
authors.initials: C
authors.lastname: Gysin
authors.affiliation: Children's Research Center, University Children's Hospital, Experimental Infectious Diseases and Cancer Research, Zurich, Switzerland.|Division of Infectious Diseases, and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Nadal
authors.affiliation: Children's Research Center, University Children's Hospital, Experimental Infectious Diseases and Cancer Research, Zurich, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lünemann
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D019002:CD56 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C490798:ARID3A protein, human; D019002:CD56 Antigen; D004268:DNA-Binding Proteins; C573415:IFNG protein, human; C522918:NCAM1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D014157:Transcription Factors; D007371:Interferon-gamma
keywords: B cells; epstein barr virus; interferon gamma; natural killer cells; secondary lymphoid organs