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

Immunity. 2020 Sep 15;53(3):548-563.e8. doi: 10.1016/j.immuni.2020.08.001. Epub 2020 Aug 27.


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.

Keywords: B cell; HIV; VRC01; affinity threshold; germinal center; germline targeting; nanoparticle; plasma cell; vaccine; valency.

Publication types

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

MeSH terms

  • Animals
  • Antibody Affinity / immunology*
  • Antigens / immunology*
  • B-Lymphocytes / immunology*
  • Binding Sites, Antibody / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Cell Proliferation / physiology
  • Germinal Center / immunology*
  • Interferon Regulatory Factors / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Plasma Cells / immunology
  • Protein Multimerization / immunology
  • Proto-Oncogene Proteins c-bcl-6 / immunology


  • Antigens
  • Bcl6 protein, mouse
  • Interferon Regulatory Factors
  • Proto-Oncogene Proteins c-bcl-6
  • interferon regulatory factor-4