Primary Human Influenza B Virus Infection Induces Cross-Lineage Hemagglutinin Stalk-Specific Antibodies Mediating Antibody-Dependent Cellular Cytoxicity

J Infect Dis. 2017 Dec 27;217(1):3-11. doi: 10.1093/infdis/jix546.


Influenza A virus (IAV) and influenza B virus (IBV) cause substantial morbidity and mortality during annual epidemics. Two distinct lineages of IBV are distinguished, based on variation in hemagglutinin (HA): B/Victoria/2/87-like (B/Vic) and B/Yamagata/16/88-like (B/Yam). Here, we show that, in humans, primary IBV infection with either lineage induces HA-specific antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. IBV infection induced antibodies specific to the HA head and stalk, but only HA stalk-specific antibodies mediated ADCC efficiently and displayed cross-reactivity with IBV of both lineages. This corresponds to recent findings that 2 points of contact between the effector and target cell (ie, HA and sialic acid, respectively, and the fragment crystallizable [Fc] domain and Fcγ receptor IIIα, respectively) are required for efficient ADCC activity and that antibodies specific for the receptor-binding site located in the head domain of HA therefore fail to mediate ADCC. Potentially, ADCC-mediating antibodies directed to the HA stalk of IBV contribute to cross-protective immunity to IBV of both lineages.

Keywords: Influenza B virus; antibodies; antibody-dependent cellular cytotoxicity; hemagglutinin; natural killer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / blood*
  • Antibody-Dependent Cell Cytotoxicity*
  • Child
  • Child, Preschool
  • Cross Reactions*
  • Cross-Sectional Studies
  • Female
  • Genotype
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Infant
  • Influenza B virus / classification
  • Influenza B virus / genetics
  • Influenza B virus / immunology*
  • Influenza, Human / immunology*
  • Male


  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus