B cells are sufficient to prime the dominant CD4+ Tfh response to Plasmodium infection

J Exp Med. 2020 Feb 3;217(2):e20190849. doi: 10.1084/jem.20190849.

Abstract

CD4+ T follicular helper (Tfh) cells dominate the acute response to a blood-stage Plasmodium infection and provide signals to direct B cell differentiation and protective antibody expression. We studied antigen-specific CD4+ Tfh cells responding to Plasmodium infection in order to understand the generation and maintenance of the Tfh response. We discovered that a dominant, phenotypically stable, CXCR5+ Tfh population emerges within the first 4 d of infection and results in a CXCR5+ CCR7+ Tfh/central memory T cell response that persists well after parasite clearance. We also found that CD4+ T cell priming by B cells was both necessary and sufficient to generate this Tfh-dominant response, whereas priming by conventional dendritic cells was dispensable. This study provides important insights into the development of CD4+ Tfh cells during Plasmodium infection and highlights the heterogeneity of antigen-presenting cells involved in CD4+ T cell priming.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Protozoan / immunology
  • Antigens, Protozoan / immunology
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Immunologic Memory
  • Lymphocyte Activation / immunology
  • Malaria / immunology*
  • Malaria / parasitology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organisms, Genetically Modified
  • Phenotype
  • Plasmodium yoelii / genetics*
  • Receptors, CCR7 / metabolism
  • Receptors, CXCR5 / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • CXCR5 protein, mouse
  • Ccr7 protein, mouse
  • Epitopes, T-Lymphocyte
  • Receptors, CCR7
  • Receptors, CXCR5