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T-bet+ B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms.
Rauch, Eileen; Amendt, Timm; Lopez Krol, Aleksandra; Lang, Fabian B; Linse, Vincent; Hohmann, Michelle; Keim, Ann-Christin; Kreutzer, Susanne; Kawengian, Kevin; Buchholz, Malte; Duschner, Philipp; Grauer, Saskia; Schnierle, Barbara; Ruhl, Andreas; Burtscher, Ingo; Dehnert, Sonja; Kuria, Chege; Kupke, Alexandra; Paul, Stephanie; Liehr, Thomas; Lechner, Marcus; Schnare, Markus; Kaufmann, Andreas; Huber, Magdalena; Winkler, Thomas H; Bauer, Stefan; Yu, Philipp.
Afiliación
  • Rauch E; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Amendt T; CSL Behring Innovation GmbH, Emil-von-Behring-Str. 76, 35041, Marburg, Germany.
  • Lopez Krol A; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Lang FB; The Francis Crick Institute, NW1 1AT, London, UK.
  • Linse V; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Hohmann M; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Keim AC; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Kreutzer S; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Kawengian K; Apollo Ventures Holding GmbH, 20457, Hamburg, Germany.
  • Buchholz M; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Duschner P; Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.
  • Grauer S; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Schnierle B; Department of Gastroenterology, Endocrinology and Metabolism, and Core Facility Small Animal Multispectral and Ultrasound Imaging, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Ruhl A; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Burtscher I; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Dehnert S; Department of Virology, Paul-Ehrlich-Institut, 63225, Langen, Germany.
  • Kuria C; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Kupke A; Department of Infection Biology, University Hospital Erlangen, 91054, Erlangen, Germany.
  • Paul S; Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
  • Liehr T; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Lechner M; Nikolaus-Fiebiger Center for Molecular Medicine, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054, Erlangen, Germany.
  • Schnare M; Institute of Virology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Kaufmann A; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Huber M; Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, 07747, Jena, Germany.
  • Winkler TH; Center for Synthetic Microbiology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Bauer S; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
  • Yu P; Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
Nat Commun ; 15(1): 1229, 2024 Feb 09.
Article en En | MEDLINE | ID: mdl-38336876
ABSTRACT
Endogenous retroviruses (ERVs) are an integral part of the mammalian genome. The role of immune control of ERVs in general is poorly defined as is their function as anti-cancer immune targets or drivers of autoimmune disease. Here, we generate mouse-strains where Moloney-Murine Leukemia Virus tagged with GFP (ERV-GFP) infected the mouse germline. This enables us to analyze the role of genetic, epigenetic and cell intrinsic restriction factors in ERV activation and control. We identify an autoreactive B cell response against the neo-self/ERV antigen GFP as a key mechanism of ERV control. Hallmarks of this response are spontaneous ERV-GFP+ germinal center formation, elevated serum IFN-γ levels and a dependency on Age-associated B cells (ABCs) a subclass of T-bet+ memory B cells. Impairment of IgM B cell receptor-signal in nucleic-acid sensing TLR-deficient mice contributes to defective ERV control. Although ERVs are a part of the genome they break immune tolerance, induce immune surveillance against ERV-derived self-antigens and shape the host immune response.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos B / Retrovirus Endógenos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos B / Retrovirus Endógenos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido