AI Article Synopsis

  • Infection and vaccination lead to the creation of antibodies against various influenza virus subtypes, but most antibodies target variable epitopes rather than conserved ones.
  • The study reveals that producing broadly reactive antibodies against flu can increase autoimmune responses in both humans and mice, worsening autoimmune diseases.
  • The findings suggest that mechanisms that promote self-tolerance are crucial in limiting these broadly reactive antibodies, which can contribute to disease when inflammation or autoimmune risks are present.

Article Abstract

Infection and vaccination repeatedly expose individuals to antigens that are conserved between influenza virus subtypes. Nevertheless, antibodies recognizing variable influenza epitopes greatly outnumber antibodies reactive against conserved epitopes. Elucidating factors contributing to the paucity of broadly reactive influenza antibodies remains a major obstacle for developing a universal influenza vaccine. Here, we report that inducing broadly reactive influenza antibodies increases autoreactive antibodies in humans and mice and exacerbates disease in four distinct models of autoimmune disease. Importantly, transferring broadly reactive influenza antibodies augments disease in the presence of inflammation or autoimmune susceptibility. Further, broadly reactive influenza antibodies spontaneously arise in mice with defects in B cell tolerance. Together, these data suggest that self-tolerance mechanisms limit the prevalence of broadly reactive influenza antibodies, which can exacerbate disease in the context of additional risk factors.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036619PMC
http://dx.doi.org/10.1016/j.celrep.2022.110482DOI Listing

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