Follicular helper T cell differentiation requires continuous antigen presentation that is independent of unique B cell signaling

Immunity. 2010 Aug 27;33(2):241-53. doi: 10.1016/j.immuni.2010.07.015. Epub 2010 Aug 5.


Effective humoral immunity depends on the support of B cell responses by T follicular helper (Tfh) cells. Although it has been proposed that Tfh cell differentiation requires T-B interactions, the relative contribution of specific populations of Ag-presenting cells remains unknown. We employed three independent strategies that compromised interactions between CD4(+) T cells and activated B cells in vivo. Whereas the expansion of CD4(+) T cells was relatively unaffected, Tfh cell differentiation was completely blocked in all scenarios. Surprisingly, augmenting antigen presentation by non-B cells rescued Tfh cell differentiation, as determined by surface phenotype, gene expression, and germinal center localization. We conclude that although Ag presentation by responding B cells is typically required for the generation of Tfh cells, this does not result from the provision of a unique B cell-derived signal, but rather because responding B cells rapidly become the primary source of antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD40 Antigens / immunology
  • Cell Differentiation*
  • Cells, Cultured
  • Gene Expression Regulation
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Proteins c-bcl-6 / immunology
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • Signal Transduction*
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / immunology*


  • CD40 Antigens
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Sh2d1a protein, mouse
  • Signaling Lymphocytic Activation Molecule Associated Protein