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T-bet+ B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms

Author

Listed:
  • Eileen Rauch

    (Philipps-Universität Marburg
    CSL Behring Innovation GmbH)

  • Timm Amendt

    (Philipps-Universität Marburg
    The Francis Crick Institute)

  • Aleksandra Lopez Krol

    (Philipps-Universität Marburg)

  • Fabian B. Lang

    (Philipps-Universität Marburg)

  • Vincent Linse

    (Philipps-Universität Marburg)

  • Michelle Hohmann

    (Philipps-Universität Marburg
    Apollo Ventures Holding GmbH)

  • Ann-Christin Keim

    (Philipps-Universität Marburg)

  • Susanne Kreutzer

    (Max-Planck-Institute for Heart and Lung Research)

  • Kevin Kawengian

    (Philipps-Universität Marburg)

  • Malte Buchholz

    (Philipps-Universität Marburg)

  • Philipp Duschner

    (Philipps-Universität Marburg)

  • Saskia Grauer

    (Philipps-Universität Marburg)

  • Barbara Schnierle

    (Paul-Ehrlich-Institut)

  • Andreas Ruhl

    (Philipps-Universität Marburg
    University Hospital Erlangen)

  • Ingo Burtscher

    (Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München)

  • Sonja Dehnert

    (Philipps-Universität Marburg)

  • Chege Kuria

    (Friedrich-Alexander Universität Erlangen-Nürnberg)

  • Alexandra Kupke

    (Philipps-Universität Marburg)

  • Stephanie Paul

    (Philipps-Universität Marburg)

  • Thomas Liehr

    (Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics)

  • Marcus Lechner

    (Philipps-Universität Marburg)

  • Markus Schnare

    (Philipps-Universität Marburg)

  • Andreas Kaufmann

    (Philipps-Universität Marburg)

  • Magdalena Huber

    (Philipps-Universität Marburg)

  • Thomas H. Winkler

    (Friedrich-Alexander Universität Erlangen-Nürnberg)

  • Stefan Bauer

    (Philipps-Universität Marburg)

  • Philipp Yu

    (Philipps-Universität Marburg)

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.

Suggested Citation

  • Eileen Rauch & Timm Amendt & Aleksandra Lopez Krol & Fabian B. Lang & Vincent Linse & Michelle Hohmann & Ann-Christin Keim & Susanne Kreutzer & Kevin Kawengian & Malte Buchholz & Philipp Duschner & Sa, 2024. "T-bet+ B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45201-6
    DOI: 10.1038/s41467-024-45201-6
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