A B cell screen against endogenous retroviruses identifies glycan-reactive IgM that recognizes a broad array of enveloped viruses

Sci Immunol. 2024 Nov 8;9(101):eadd6608. doi: 10.1126/sciimmunol.add6608. Epub 2024 Nov 8.

Abstract

Endogenous retroviruses (ERVs), comprising a substantial portion of the vertebrate genome, are remnants of ancient genetic invaders. ERVs with near-intact coding potential reactivate in B cell-deficient mice. To study how B cells contribute to host anti-ERV immunity, we used an antigen-baiting strategy to enrich B cells reactive to ERV surface antigens. We identified ERV-reactive B-1 cells expressing germline-encoded natural IgM antibodies in naïve mice, the level of which further increases upon innate immune sensor stimulation. B cell receptor repertoire profiling of ERV-reactive B-1 cells revealed increased usage of the Igh VH gene that gives rise to glycan-specific antibodies targeting terminal N-acetylglucosamine moieties on ERV glycoproteins, which further engage the complement pathway to mediate anti-ERV responses. These same antibodies also recognize glycoproteins of other enveloped viruses but not self-proteins. These results reveal an innate antiviral mechanism of germline-encoded antibodies with broad reactivity to enveloped viruses, which constitutes a natural antibody repertoire capable of preventing the emergence of infectious ERVs.

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • B-Lymphocytes* / immunology
  • Endogenous Retroviruses* / immunology
  • Immunoglobulin M* / immunology
  • Mice
  • Mice, Inbred C57BL
  • Polysaccharides* / immunology

Substances

  • Immunoglobulin M
  • Polysaccharides
  • Antibodies, Viral