The strength of BCR signaling shapes terminal development of follicular helper T cells in mice

Eur J Immunol. 2017 Aug;47(8):1295-1304. doi: 10.1002/eji.201746952. Epub 2017 Jul 3.


Antibody production is key for effective immune response and relies on follicular helper T (Tfh) cells. B cell-Tfh cell interactions result either in an extra-follicular low affinity B-cell response or in germinal center reactions producing high-affinity memory B cells and long-lived plasma cells. As Tfh cells influence B-cell commitment, it also became clear that B cells influence these interactions in ways that still remain unresolved. We observed that strong BCR signals decreased Tfh-cell differentiation in vitro, which correlated with decreased expression of ICOS-L at the surface of stimulated B cells. Further, we comprehensively demonstrated that ICOS-L expression correlated with the level of Tfh differentiation irrespective of antigen presentation at the surface of activated B cells. Our in vivo experiments could show that immunization with a high-affinity antigen for B cells resulted in much less Tfh development than immunization with low-affinity antigen. Furthermore, blocking ICOS-L in vivo inhibited Tfh development when using low-affinity antigen. Altogether, these results indicate that BCR affinity shapes Tfh-cell development in part through ICOS/ICOS-L interactions. Ultimately, we reveal new depths in the B cell-Tfh cell crosstalk that could eventually result in better vaccine protocols.

Keywords: Antigen receptors; B cells; BCR; Follicular helper T cells; ICOS-L; Immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Differentiation
  • Flow Cytometry
  • Germinal Center / immunology
  • Inducible T-Cell Co-Stimulator Ligand / genetics
  • Inducible T-Cell Co-Stimulator Ligand / metabolism*
  • Lymphocyte Activation*
  • Mice
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, B-Cell / metabolism*
  • Receptors, CXCR5 / genetics
  • Receptors, CXCR5 / immunology
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Icosl protein, mouse
  • Inducible T-Cell Co-Stimulator Ligand
  • Receptors, Antigen, B-Cell
  • Receptors, CXCR5