| Autor: |
Yang, Yexin, Treger, Rebecca S., Hernandez-Bird, Juan, Lu, Peiwen, Mao, Tianyang, Iwasaki, Akiko |
| Zdroj: |
Science Immunology; 2024, Vol. 9 Issue 101, p1-17, 17p |
| Abstrakt: |
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. Editor's summary: Control of endogenous retrovirus (ERV) reactivation is mediated through a T cell–independent (TI) B cell response, but precisely how B cells mediate surveillance and prevention of ERV reactivation is unclear. Yang et al. developed an antigen-baiting assay to detect ERV-reactive B cells in mice, identifying that peritoneal B-1 cells expressing germline-encoded IgM were the major source of anti-ERV antibodies. A monoclonal antibody produced by ERV-reactive B-1 cells recognized not only terminal N-acetylglucosamine (GlcNAc) on the surface of ERV glycoproteins but also GlcNAc found on a broader range of viral glycoproteins and enveloped viruses. These results demonstrate that recognition of viral glycans by natural antibodies is a general innate antiviral mechanism. —Hannah Isles [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
