Polyreactive Broadly Neutralizing B cells Are Selected to Provide Defense against Pandemic Threat Influenza Viruses

Jenna J. Guthmiller, Linda Yu Ling Lan, Monica L. Fernández-Quintero, Julianna Han, Henry A. Utset, Dalia J. Bitar, Natalie J. Hamel, Olivia Stovicek, Lei Li, Micah Tepora, Carole Henry, Karlynn E. Neu, Haley L. Dugan, Marta T. Borowska, Yao Qing Chen, Sean T.H. Liu, Christopher T. Stamper, Nai Ying Zheng, Min Huang, Anna Karin E. PalmAdolfo García-Sastre, Raffael Nachbagauer, Peter Palese, Lynda Coughlan, Florian Krammer, Andrew B. Ward, Klaus R. Liedl, Patrick C. Wilson

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


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 analyzing more than 500 monoclonal antibodies (mAbs) derived from B cells induced by numerous influenza virus vaccines and infections, we found mAbs targeting conserved neutralizing influenza virus hemagglutinin epitopes were polyreactive. Polyreactive mAbs were preferentially induced by novel viral exposures due to their broad viral binding breadth. Polyreactivity augmented 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 that polyreactivity is a beneficial feature of antibodies targeting conserved epitopes.

Original languageEnglish
Pages (from-to)1230-1244.e5
Issue number6
StatePublished - 15 Dec 2020


  • antibody flexibility
  • broadly neutralizing antibodies
  • influenza viruses
  • monoclonal antibodies
  • polyreactivity


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