title: Suppression of Fcγ-receptor-mediated antibody effector function during persistent viral infection.
abstract: Understanding how viruses subvert host immunity and persist is essential for developing strategies to eliminate infection. T cell exhaustion during chronic viral infection is well described, but effects on antibody-mediated effector activity are unclear. Herein, we show that increased amounts of immune complexes generated in mice persistently infected with lymphocytic choriomeningitis virus (LCMV) suppressed multiple Fcγ-receptor (FcγR) functions. The high amounts of immune complexes suppressed antibody-mediated cell depletion, therapeutic antibody-killing of LCMV infected cells and human CD20-expressing tumors, as well as reduced immune complex-mediated cross-presentation to T cells. Suppression of FcγR activity was not due to inhibitory FcγRs or high concentrations of free antibody, and proper FcγR functions were restored when persistently infected mice specifically lacked immune complexes. Thus, we identify a mechanism of immunosuppression during viral persistence with implications for understanding effective antibody activity aimed at pathogen control.
authors: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
authors: Douglas H
authors: DH
authors: Yamada
authors: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
authors: Heidi
authors: H
authors: Elsaesser
authors: Institute of Genetics, Department of Biology, University of Erlangen-Nürnberg, Erwin-Rommelstrasse 3, 91058, Erlangen, Germany.
authors: Anja
authors: A
authors: Lux
authors: Division of Hematology & Oncology, Department of Medicine, and Department of Pathology & Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.
authors: John M
authors: JM
authors: Timmerman
authors: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
authors: Sherie L
authors: SL
authors: Morrison
authors: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors: Juan Carlos
authors: JC
authors: de la Torre
authors: Institute of Genetics, Department of Biology, University of Erlangen-Nürnberg, Erwin-Rommelstrasse 3, 91058, Erlangen, Germany.
authors: Falk
authors: F
authors: Nimmerjahn
authors: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. Electronic address: dbrooks@microbio.ucla.edu.
authors: David G
authors: DG
authors: Brooks
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; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D057131:Immune Evasion / Q000276:immunology*; D007108:Immune Tolerance / 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; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis / Q000276:immunology; D017452:Receptors, IgG / Q000037:antagonists & inhibitors* / Q000276:immunology; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D018951:Antigens, CD20; D007155:Immunologic Factors; D017452:Receptors, IgG; D000069283:Rituximab