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Clonal replacement sustains long-lived germinal centers primed by respiratory viruses.
de Carvalho, Renan V H; Ersching, Jonatan; Barbulescu, Alexandru; Hobbs, Alvaro; Castro, Tiago B R; Mesin, Luka; Jacobsen, Johanne T; Phillips, Brooke K; Hoffmann, Hans-Heinrich; Parsa, Roham; Canesso, Maria Cecilia C; Nowosad, Carla R; Feng, Allan; Leist, Sarah R; Baric, Ralph S; Yang, Emily; Utz, P J; Victora, Gabriel D.
Afiliação
  • de Carvalho RVH; Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
  • Ersching J; Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
  • Barbulescu A; Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY, USA.
  • Hobbs A; Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
  • Castro TBR; Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA; Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA.
  • Mesin L; Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
  • Jacobsen JT; Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
  • Phillips BK; Rutgers Robert Wood Johnson Medical School and Princeton University MD/PhD Program, Piscataway, NJ, USA.
  • Hoffmann HH; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
  • Parsa R; Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA.
  • Canesso MCC; Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA; Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA.
  • Nowosad CR; Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA; Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA.
  • Feng A; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Yang E; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Utz PJ; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Victora GD; Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA. Electronic address: victora@rockefeller.edu.
Cell ; 186(1): 131-146.e13, 2023 01 05.
Article em En | MEDLINE | ID: mdl-36565697
ABSTRACT
Germinal centers (GCs) form in secondary lymphoid organs in response to infection and immunization and are the source of affinity-matured B cells. The duration of GC reactions spans a wide range, and long-lasting GCs (LLGCs) are potentially a source of highly mutated B cells. We show that rather than consisting of continuously evolving B cell clones, LLGCs elicited by influenza virus or SARS-CoV-2 infection in mice are sustained by progressive replacement of founder clones by naive-derived invader B cells that do not detectably bind viral antigens. Rare founder clones that resist replacement for long periods are enriched in clones with heavily mutated immunoglobulins, including some with very high affinity for antigen, that can be recalled by boosting. Our findings reveal underappreciated aspects of the biology of LLGCs generated by respiratory virus infection and identify clonal replacement as a potential constraint on the development of highly mutated antibodies within these structures.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por Vírus de RNA / Linfócitos B / Centro Germinativo Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por Vírus de RNA / Linfócitos B / Centro Germinativo Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article