Requirement for memory B-cell activation in protection from heterologous influenza virus reinfection

Int Immunol. 2019 Nov 8;31(12):771-779. doi: 10.1093/intimm/dxz049.

Abstract

While two memory compartments, memory B cells and long-lived plasma cells, are thought to contribute to the successful establishment of memory recall responses, the unique roles of each cellular compartment are still unclear. Herein, by tracing influenza anti-hemagglutinin (HA)-specific antibodies in mice, we demonstrate that pre-existing antibodies secreted by long-lived plasma cells are essential for protection from reinfection with the same influenza virus, whereas protection from secondary infection with an antigenically distinct influenza virus requires memory B-cell activation. These activated memory B cells were largely specific for the conserved HA stem region, and generated sufficient levels of antibodies for protection from heterologous reinfection. Given that the anti-stem plasmablasts derived from the memory B cells were higher affinity than those from naive B cells, our results suggest that maturation of anti-stem memory B cells during primary influenza infection and their subsequent activation are required for protection from reinfection by mutant viruses.

Keywords: antibody; cross-reactive; immunity; infection; virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Immunologic Memory / immunology*
  • Lymphocyte Activation / immunology*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Orthomyxoviridae / immunology*
  • Orthomyxoviridae / physiology*