Polyreactive Broadly Neutralizing B Cells are Selected to Provide Defense Against Pandemic Threat Influenza Viruses
43 Pages Posted: 30 Jun 2020 Sneak Peek Status: Under ReviewMore...
Polyreactivity is the ability of a single antibody to bind to multiple molecularly distinct antigens and is a common feature of antibodies induced upon pathogen exposure. However, little is known about the role of polyreactivity during anti-influenza virus antibody responses. By comprehensively analyzing more than 500 monoclonal antibodies (mAbs) derived from B cells induced by numerous influenza virus vaccines and infections, we find mAbs targeting conserved neutralizing influenza virus hemagglutinin epitopes are polyreactive. Polyreactive mAbs are preferentially induced by novel viral exposures due to their broad viral binding breadth. Polyreactivity augments mAb viral binding strength by increasing antibody flexibility, allowing for adaption to imperfectly conserved epitopes. Lastly, we found affinity-matured polyreactive B cells were typically derived from germline polyreactive B cells that were preferentially selected to participate in B cell responses over time. Together, our data reveal polyreactivity is a beneficial feature of antibodies targeting conserved epitopes.
Keywords: Polyreactivity, broadly neutralizing antibodies, influenza viruses, monoclonal antibodies
Suggested Citation: Suggested Citation