Phenotypic Tfh development promoted by CXCR5-controlled re-localization and IL-6 from radiation-resistant cells

Protein Cell. 2015 Nov;6(11):825-32. doi: 10.1007/s13238-015-0210-0.


How follicular T-helper (Tfh) cells develop is incompletely understood. We find that, upon antigen exposure in vivo, both naïve and antigen-experienced T cells sequentially upregulate CXCR5 and Bcl6 within the first 24 h, relocate to the T-B border, and give rise to phenotypic Bcl6(+)CXCR5(+) Tfh cells before the first cell division. CXCR5 upregulation is more dependent on ICOS costimulation than that of Bcl6, and early Bcl6 induction requires T-cell expression of CXCR5 and, presumably, relocation toward the follicle. This early and rapid upregulation of CXCR5 and Bcl6 depends on IL-6 produced by radiation-resistant cells. These results suggest that a Bcl6(hi)CXCR5(hi) phenotype does not automatically define a Tfh lineage but might reflect a state of antigen exposure and non-commitment to terminal effector fates and that niches in the T-B border and/or the follicle are important for optimal Bcl6 induction and maintenance.

Keywords: Bcl6; CXCR5; IL-6; Tfh; radiation-resistant cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD40 Ligand / metabolism
  • Cell Differentiation / physiology
  • DNA-Binding Proteins / metabolism
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Interleukin-6 / metabolism*
  • Mice
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, CXCR5 / metabolism*
  • T-Lymphocytes, Helper-Inducer / metabolism


  • Bcl6 protein, mouse
  • DNA-Binding Proteins
  • Icos protein, mouse
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukin-6
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, CXCR5
  • CD40 Ligand