Cell Reports (Jan 2020)

Chronic Viral Infection Promotes Efficient Germinal Center B Cell Responses

  • Bénédict Fallet,
  • Yi Hao,
  • Marianna Florova,
  • Karen Cornille,
  • Alba Verge de los Aires,
  • Giulia Girelli Zubani,
  • Yusuf I. Ertuna,
  • Victor Greiff,
  • Ulrike Menzel,
  • Karim Hammad,
  • Doron Merkler,
  • Sai T. Reddy,
  • Jean-Claude Weill,
  • Claude-Agnès Reynaud,
  • Daniel D. Pinschewer

Journal volume & issue
Vol. 30, no. 4
pp. 1013 – 1026.e7

Abstract

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Summary: Persistent viral infections subvert key elements of adaptive immunity. To compare germinal center (GC) B cell responses in chronic and acute lymphocytic choriomeningitis virus infection, we exploit activation-induced deaminase (AID) fate-reporter mice and perform adoptive B cell transfer experiments. Chronic infection yields GC B cell responses of higher cellularity than acute infections do, higher memory B cell and antibody secreting cell output for longer periods of time, a better representation of the late B cell repertoire in serum immunoglobulin, and higher titers of protective neutralizing antibodies. GC B cells of chronically infected mice are similarly hypermutated as those emerging from acute infection. They efficiently adapt to viral escape variants and even in hypermutation-impaired AID mutant mice, chronic infection selects for GC B cells with hypermutated B cell receptors (BCRs) and neutralizing antibody formation. These findings demonstrate that, unlike for CD8+ T cells, chronic viral infection drives a functional, productive, and protective GC B cell response. : Fallet et al. used AID fate-mapping to compare germinal center responses to chronic and acute viral infection. Germinal center B cells in chronic infection hypermutate efficiently, adapt to viral variants, and yield more antibody-secreting cells and memory B cells for longer time periods than found in acute infection, enabling neutralizing antibody formation. Keywords: chronic viral infection, germinal center B cells, neutralizing antibody, affinity maturation, lymphocytic choriomeningitis virus, LCMV, AID, memory B cell, antibody-secreting cell