Temporal dynamics of persistent germinal centers and memory B cell differentiation following respiratory virus infection

Cell Rep. 2021 Nov 9;37(6):109961. doi: 10.1016/j.celrep.2021.109961.

Abstract

Following infection or immunization, memory B cells (MBCs) and long-lived plasma cells provide humoral immunity that can last for decades. Most principles of MBC biology have been determined with hapten-protein carrier models or fluorescent protein immunizations. Here, we examine the temporal dynamics of the germinal center (GC) B cell and MBC response following mouse influenza A virus infection. We find that antiviral B cell responses within the lung-draining mediastinal lymph node (mLN) and the spleen are distinct in regard to duration, enrichment for antigen-binding cells, and class switching dynamics. While splenic GCs dissolve after 6 weeks post-infection, mLN hemagglutinin-specific (HA+) GCs can persist for 22 weeks. Persistent GCs continuously differentiate MBCs, with "peak" and "late" GCs contributing equal numbers of HA+ MBCs to the long-lived compartment. Our findings highlight critical aspects of persistent GC responses and MBC differentiation following respiratory virus infection with direct implications for developing effective vaccination strategies.

Keywords: antiviral; germinal center; influenza A virus; memory B cell; respiratory virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • Cell Differentiation
  • Female
  • Germinal Center / immunology*
  • Immunologic Memory*
  • Influenza A virus / physiology*
  • Lymphocyte Activation
  • Male
  • Memory B Cells / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology
  • T-Box Domain Proteins / physiology*
  • T-bet Transcription Factor

Substances

  • Antibodies, Viral
  • T-Box Domain Proteins
  • T-bet Transcription Factor