Chronic Viral Infection Promotes Efficient Germinal Center B Cell Responses
Bénédict Fallet,
Yi Hao,
Marianna Florova,
Karen Cornille,
Alba Verge de los Aires,
Giulia Girelli Zubani,
Yusuf I. Ertuna,
Victor Greiff,
Ulrike Menzel,
Karim Hammad,
Doron Merkler,
Sai T. Reddy,
Jean-Claude Weill,
Claude-Agnès Reynaud,
Daniel D. Pinschewer
Affiliations
Bénédict Fallet
Department of Biomedicine, Division of Experimental Virology, University of Basel, Haus Petersplatz, 4009 Basel, Switzerland
Yi Hao
Development of the Immune System, Institut Necker-Enfants Malades, Institut National de la Santé et de la Recherche Médicale, U1151-Centre National de la Recherche Scientifique, UMR 8253, Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Marianna Florova
Department of Biomedicine, Division of Experimental Virology, University of Basel, Haus Petersplatz, 4009 Basel, Switzerland
Karen Cornille
Department of Biomedicine, Division of Experimental Virology, University of Basel, Haus Petersplatz, 4009 Basel, Switzerland
Alba Verge de los Aires
Development of the Immune System, Institut Necker-Enfants Malades, Institut National de la Santé et de la Recherche Médicale, U1151-Centre National de la Recherche Scientifique, UMR 8253, Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Giulia Girelli Zubani
Development of the Immune System, Institut Necker-Enfants Malades, Institut National de la Santé et de la Recherche Médicale, U1151-Centre National de la Recherche Scientifique, UMR 8253, Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Yusuf I. Ertuna
Department of Biomedicine, Division of Experimental Virology, University of Basel, Haus Petersplatz, 4009 Basel, Switzerland
Victor Greiff
Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland; Department of Immunology, University of Oslo, Oslo, Norway
Ulrike Menzel
Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland
Karim Hammad
Department of Pathology and Immunology, Division of Clinical Pathology, University & University Hospital of Geneva, Geneva, Switzerland
Doron Merkler
Department of Pathology and Immunology, Division of Clinical Pathology, University & University Hospital of Geneva, Geneva, Switzerland
Sai T. Reddy
Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland
Jean-Claude Weill
Development of the Immune System, Institut Necker-Enfants Malades, Institut National de la Santé et de la Recherche Médicale, U1151-Centre National de la Recherche Scientifique, UMR 8253, Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Claude-Agnès Reynaud
Development of the Immune System, Institut Necker-Enfants Malades, Institut National de la Santé et de la Recherche Médicale, U1151-Centre National de la Recherche Scientifique, UMR 8253, Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Daniel D. Pinschewer
Department of Biomedicine, Division of Experimental Virology, University of Basel, Haus Petersplatz, 4009 Basel, Switzerland; Corresponding author
Summary: Persistent viral infections subvert key elements of adaptive immunity. To compare germinal center (GC) B cell responses in chronic and acute lymphocytic choriomeningitis virus infection, we exploit activation-induced deaminase (AID) fate-reporter mice and perform adoptive B cell transfer experiments. Chronic infection yields GC B cell responses of higher cellularity than acute infections do, higher memory B cell and antibody secreting cell output for longer periods of time, a better representation of the late B cell repertoire in serum immunoglobulin, and higher titers of protective neutralizing antibodies. GC B cells of chronically infected mice are similarly hypermutated as those emerging from acute infection. They efficiently adapt to viral escape variants and even in hypermutation-impaired AID mutant mice, chronic infection selects for GC B cells with hypermutated B cell receptors (BCRs) and neutralizing antibody formation. These findings demonstrate that, unlike for CD8+ T cells, chronic viral infection drives a functional, productive, and protective GC B cell response. : Fallet et al. used AID fate-mapping to compare germinal center responses to chronic and acute viral infection. Germinal center B cells in chronic infection hypermutate efficiently, adapt to viral variants, and yield more antibody-secreting cells and memory B cells for longer time periods than found in acute infection, enabling neutralizing antibody formation. Keywords: chronic viral infection, germinal center B cells, neutralizing antibody, affinity maturation, lymphocytic choriomeningitis virus, LCMV, AID, memory B cell, antibody-secreting cell