Rauch, E.* ; Amendt, T.* ; Lopez Krol, A.* ; Lang, F.B.* ; Linse, V.* ; Hohmann, M.* ; Keim, A.C.* ; Kreutzer, S.* ; Kawengian, K.* ; Buchholz, M.* ; Duschner, P.* ; Grauer, S.* ; Schnierle, B.* ; Ruhl, A.* ; Burtscher, I. ; Dehnert, S.* ; Kuria, C.* ; Kupke, A.* ; Paul, S.* ; Liehr, T.* ; Lechner, M.* ; Schnare, M.* ; Kaufmann, A.* ; Huber, M.* ; Winkler, T.H.* ; Bauer, S.* ; Yu, P.*
T-bet+ B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms.
Nat. Commun. 15:1229 (2024)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Murine Leukemia-virus; Toll-like Receptors; Ifn-gamma Receptor; Immune-responses; T-bet; Mice; Antibody; Rna; Ige; Generation
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2024
Prepublished im Jahr
0
HGF-Berichtsjahr
2024
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 15,
Heft: 1,
Seiten: ,
Artikelnummer: 1229
Supplement: ,
Reihe
Verlag
Nature Publishing Group
Verlagsort
London
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30201 - Metabolic Health
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-502300-001
Förderungen
Open Access Publishing Fund of Philipps-Universitaet Marburg
DFG
Copyright
Erfassungsdatum
2024-02-12