The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding

Nat Immunol. 2009 Apr;10(4):375-84. doi: 10.1038/ni.1704. Epub 2009 Mar 1.


How follicular helper T cells (T(FH) cells) differentiate to regulate B cell immunity is critical for effective protein vaccination. Here we define three transcription factor T-bet-expressing antigen-specific effector helper T cell subsets with distinguishable function, migratory properties and developmental programming in vivo. Expression of the transcriptional repressor Blimp-1 distinguished T zone 'lymphoid' effector helper T cells (CD62L(hi)CCR7(hi)) from CXCR5(lo) 'emigrant' effector helper T cells and CXCR5(hi) 'resident' T(FH) cells expressing the transcriptional repressor Bcl-6 (CD62L(lo)CCR7(lo)). We then show by adoptive transfer and intact polyclonal responses that helper T cells with the highest specific binding of peptide-major histocompatibility complex class II and the most restricted T cell antigen receptor junctional diversity 'preferentially' developed into the antigen-specific effector T(FH) compartment. Our studies demonstrate a central function for differences in the binding strength of the T cell antigen receptor in the antigen-specific mechanisms that 'program' specialized effector T(FH) function in vivo.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adoptive Transfer
  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • Cytokines / biosynthesis
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Histocompatibility Antigens Class II / metabolism
  • L-Selectin / immunology
  • Lymph Nodes / immunology
  • Mice
  • Mice, Transgenic
  • Positive Regulatory Domain I-Binding Factor 1
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • T-Box Domain Proteins / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-Lymphocytes, Helper-Inducer / transplantation
  • Transcription Factors / biosynthesis
  • Transcription Factors / immunology


  • Adjuvants, Immunologic
  • Bcl6 protein, mouse
  • Cytokines
  • DNA-Binding Proteins
  • Histocompatibility Antigens Class II
  • Prdm1 protein, mouse
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, Antigen, T-Cell
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transcription Factors
  • L-Selectin
  • Positive Regulatory Domain I-Binding Factor 1