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 role as anti-cancer immune targets or drivers of autoimmune disease. Here, we generated mouse-strains where Moloney-Murine Leukemia Virus tagged with GFP (ERV-GFP) infected the murine germline. This enabled us to analyze the role of genetic, epigenetic and cell intrinsic restriction factors in ERV activation and control. We identified 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 T-bet+ 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 hosts immune response.