Multifaceted Effects of Antigen Valency on B Cell Response Composition and Differentiation In Vivo

Yu Kato, Robert K. Abbott, Brian L. Freeman, Sonya Haupt, Bettina Groschel, Murillo Silva, Sergey Menis, Darrell J. Irvine, William R. Schief, Shane Crotty

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

How antigen valency affects B cells in vivo during immune responses is not well understood. Here, using HIV immunogens with defined valencies ranging from 1 to 60, we investigated the role of antigen valency during different phases of B cell responses in vivo. Highly multimerized immunogens preferentially rapidly activated cognate B cells, with little affinity discrimination. This led to strong early induction of the transcription factors IRF4 (interferon regulatory factor 4) and Bcl6, driving both early extrafollicular plasma cell and germinal center responses, in a CD4+ T-cell-dependent manner, involving B cells with a broad range of affinities. Low-valency antigens induced smaller effector B cell responses, with preferential recruitment of high-affinity B cells. Thus, antigen valency has multifaceted effects on B cell responses and can dictate affinity thresholds and competitive landscapes for B cells in vivo, with implications for vaccine design.

Original languageEnglish (US)
Pages (from-to)548-563.e8
JournalImmunity
Volume53
Issue number3
DOIs
StatePublished - Sep 15 2020
Externally publishedYes

Keywords

  • B cell
  • HIV
  • VRC01
  • affinity threshold
  • germinal center
  • germline targeting
  • nanoparticle
  • plasma cell
  • vaccine
  • valency

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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