title: Antibody effector functions mediated by Fcγ-receptors are compromised during persistent viral infection.
abstract: T cell dysfunction is well documented during chronic viral infections but little is known about functional abnormalities in humoral immunity. Here we report that mice persistently infected with lymphocytic choriomeningitis virus (LCMV) exhibit a severe defect in Fcγ-receptor (FcγR)-mediated antibody effector functions. Using transgenic mice expressing human CD20, we found that chronic LCMV infection impaired the depletion of B cells with rituximab, an anti-CD20 antibody widely used for the treatment of B cell lymphomas. In addition, FcγR-dependent activation of dendritic cells by agonistic anti-CD40 antibody was compromised in chronically infected mice. These defects were due to viral antigen-antibody complexes and not the chronic infection per se, because FcγR-mediated effector functions were normal in persistently infected mice that lacked LCMV-specific antibodies. Our findings have implications for the therapeutic use of antibodies and suggest that high levels of pre-existing immune complexes could limit the effectiveness of antibody therapy in humans.
authors: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Andreas
authors: A
authors: Wieland
authors: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA.
authors: Rangaiah
authors: R
authors: Shashidharamurthy
authors: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Alice O
authors: AO
authors: Kamphorst
authors: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Jin-Hwan
authors: JH
authors: Han
authors: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Rachael D
authors: RD
authors: Aubert
authors: Glycotechnology Core Resources, University of California at San Diego, La Jolla, CA 92093, USA.
authors: Biswa P
authors: BP
authors: Choudhury
authors: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA.
authors: Sean R
authors: SR
authors: Stowell
authors: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Junghwa
authors: J
authors: Lee
authors: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: George A
authors: GA
authors: Punkosdy
authors: Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors: Mark J
authors: MJ
authors: Shlomchik
authors: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA.
authors: Periasamy
authors: P
authors: Selvaraj
authors: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: rahmed@emory.edu.
authors: Rafi
authors: R
authors: Ahmed
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D000914:Antibodies, Viral / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D018951:Antigens, CD20 / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006942:Hypergammaglobulinemia / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017452:Receptors, IgG / Q000276:immunology*; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D018951:Antigens, CD20; D019013:CD40 Antigens; D007155:Immunologic Factors; D017452:Receptors, IgG; D000069283:Rituximab