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

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

SUBMITTER: Rauch E 

PROVIDER: S-EPMC10858178 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature