| First Author | Rauch E | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 1229 |
| PubMed ID | 38336876 | Mgi Jnum | J:360439 |
| Mgi Id | MGI:7594939 | Doi | 10.1038/s41467-024-45201-6 |
| Citation | Rauch E, et al. (2024) T-bet(+) B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms. Nat Commun 15(1):1229 |
| abstractText | 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-gamma 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. |
