Monocyte-derived dendritic cells promote T follicular helper cell differentiation

EMBO Mol Med. 2014 May;6(5):590-603. doi: 10.1002/emmm.201403841.


To be effective, protein priming must induce the development of a distinct lineage of CD4(+) T cells named T follicular helper (Tfh) cells, which regulate the differentiation of high-affinity memory B cells and long-lived plasma cells. In this context, we tested how adjuvantation with CpG, the Toll-like receptor 9 agonist used in clinics, contributes to antigen-specific T-cell-dependent B-cell responses in vivo. We found that addition of CpG to other vaccine adjuvant increased the differentiation of antigen-specific Tfh cells without changing the overall magnitude of the T-cell response. This phenomenon correlated with an enhancement of the germinal centre reaction, antigen-specific plasma cells and circulating antibodies. We comprehensively demonstrated that, in addition to the classical Tfh-cell differentiation mediated by conventional DC, the promoting effect due to CpG was orchestrated in vivo by antigen presentation and IL-6 secreted by monocyte-derived dendritic cells (DC) as shown in their absence. Thus, while conventional DC initiate T-cell responses, targeting monocyte-derived DC specifically enhances the Tfh programme needed to regulate high-affinity B-cell protection in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antibodies / blood
  • Antigen Presentation
  • B-Lymphocytes / immunology
  • Cell Differentiation*
  • Dendritic Cells / immunology*
  • Germinal Center / cytology
  • Germinal Center / physiology
  • Interleukin-6 / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligodeoxyribonucleotides / pharmacology*
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Plasma Cells / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / physiology*
  • Toll-Like Receptors / agonists
  • Toll-Like Receptors / immunology


  • Adjuvants, Immunologic
  • Antibodies
  • CPG-oligonucleotide
  • Interleukin-6
  • Oligodeoxyribonucleotides
  • Toll-Like Receptors
  • Ovalbumin