Chronic Viral Infection Promotes Efficient Germinal Center B Cell Responses.

Autor: Fallet B; Department of Biomedicine, Division of Experimental Virology, University of Basel, Haus Petersplatz, 4009 Basel, Switzerland., Hao Y; 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., Florova M; Department of Biomedicine, Division of Experimental Virology, University of Basel, Haus Petersplatz, 4009 Basel, Switzerland., Cornille K; Department of Biomedicine, Division of Experimental Virology, University of Basel, Haus Petersplatz, 4009 Basel, Switzerland., de Los Aires AV; 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., Girelli Zubani G; 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., Ertuna YI; Department of Biomedicine, Division of Experimental Virology, University of Basel, Haus Petersplatz, 4009 Basel, Switzerland., Greiff V; Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland; Department of Immunology, University of Oslo, Oslo, Norway., Menzel U; Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland., Hammad K; Department of Pathology and Immunology, Division of Clinical Pathology, University & University Hospital of Geneva, Geneva, Switzerland., Merkler D; Department of Pathology and Immunology, Division of Clinical Pathology, University & University Hospital of Geneva, Geneva, Switzerland., Reddy ST; Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland., Weill JC; 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., Reynaud CA; 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., Pinschewer DD; Department of Biomedicine, Division of Experimental Virology, University of Basel, Haus Petersplatz, 4009 Basel, Switzerland. Electronic address: daniel.pinschewer@unibas.ch.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2020 Jan 28; Vol. 30 (4), pp. 1013-1026.e7.
DOI: 10.1016/j.celrep.2019.12.023
Abstrakt: 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.
Competing Interests: Declaration of Interests D.D.P. is a founder, shareholder, and consultant and serves as chief scientific officer of Hookipa Pharma Inc., which is commercializing arenavirus-based vector technology. D.M. and D.D.P. are inventors on patents describing arenavirus-based vector technology. The remaining authors declare no competing interests.
(Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE