title: Epstein-Barr virus-infected B cells of males with the X-linked lymphoproliferative syndrome stimulate and are susceptible to T-cell-mediated lysis.
abstract: Primary infection with the Epstein-Barr virus (EBV) results in fatal infectious mononucleosis in up to 70% of males affected by the X-linked lymphoproliferative syndrome (XLP). This rare disease is often associated with diverse natural killer (NK)-, B- and T-cell deficiencies. We describe experiments testing whether the B lymphocytes of affected males play a role in the pathogenesis of XLP due to a low susceptibility to T-cell-mediated immunity. Using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry we detected in these B cells the expression of viral proteins EBNA-1, EBNA-2, EBNA-3A, EBNA-3C, LMP-1 and LMP-2A, which provide targets for cytotoxic T cells. Major histocompatibility complex (MHC) class I, MHC class II and the B7 costimulatory molecule were present on the cell surface. Accordingly, the EBV-infected B cells were lysed in 51Cr-release assays by T lymphocytes sharing MHC determinants with the targets. This MHC-restricted and specific lysis was confirmed in competition experiments using MHC-specific monoclonal antibodies (MAbs) and synthetic peptides. XLP-derived LCLs could also induce MHC class I-restricted memory and cytotoxic T lymphocytes. Thus, these XLP-derived B cells resembled normal LCIs in vitro with respect to induction of EBV-specific cytotoxic T cells (CTL), the ability to present EB viral antigens and the susceptibility to EBV-specific and MHC-restricted CTL-mediated killing. The failure of the immune system to eliminate these virus-infected B cells in XLP is clearly not caused by a B-cell-specific defect.
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Jäger
authors.forename: G
authors.initials: G
authors.lastname: Benninger-Döring
authors.forename: N
authors.initials: N
authors.lastname: Prang
authors.forename: B S
authors.initials: BS
authors.lastname: Sylla
authors.forename: B
authors.initials: B
authors.lastname: Laumbacher
authors.forename: R
authors.initials: R
authors.lastname: Wank
authors.forename: H
authors.initials: H
authors.lastname: Wolf
authors.forename: F
authors.initials: F
authors.lastname: Schwarzmann
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D018122:B7-1 Antigen / Q000096:biosynthesis; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology; D059870:HLA-A11 Antigen; D006566:Herpesviridae Infections / Q000276:immunology* / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007244:Infectious Mononucleosis / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000821:virology*; D008297:Male; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014158:Transcription, Genetic; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D018122:B7-1 Antigen; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D000939:Epitopes; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D014763:Viral Matrix Proteins