Germinal-center development of memory B cells driven by IL-9 from follicular helper T cells

Nat Immunol. 2017 Aug;18(8):921-930. doi: 10.1038/ni.3788. Epub 2017 Jun 26.


Germinal centers (GCs) support high-affinity, long-lived humoral immunity. How memory B cells develop in GCs is not clear. Through the use of a cell-cycle-reporting system, we identified GC-derived memory precursor cells (GC-MP cells) that had quit cycling and reached G0 phase while in the GC, exhibited memory-associated phenotypes with signs of affinity maturation and localized toward the GC border. After being transferred into adoptive hosts, GC-MP cells reconstituted a secondary response like genuine memory B cells. GC-MP cells expressed the interleukin 9 (IL-9) receptor and responded to IL-9. Acute treatment with IL-9 or antibody to IL-9 accelerated or retarded the positioning of GC-MP cells toward the GC edge and exit from the GC, and enhanced or inhibited the development of memory B cells, which required B cell-intrinsic responsiveness to IL-9. Follicular helper T cells (TFH cells) produced IL-9, and deletion of IL-9 from T cells or, more specifically, from GC TFH cells led to impaired memory formation of B cells. Therefore, the GC development of memory B cells is promoted by TFH cell-derived IL-9.

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / drug effects
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Knockdown Techniques
  • Germinal Center / immunology*
  • Immunologic Memory / drug effects
  • Immunologic Memory / immunology*
  • In Vitro Techniques
  • Interleukin-9 / immunology*
  • Interleukin-9 / pharmacology
  • Lymphoid Tissue
  • Mice
  • Mice, Knockout
  • Real-Time Polymerase Chain Reaction
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Interleukin-9