IL-9 receptor signaling in memory B cells regulates humoral recall responses

Nat Immunol. 2018 Sep;19(9):1025-1034. doi: 10.1038/s41590-018-0177-0. Epub 2018 Aug 6.

Abstract

Memory B cells (Bmem cells) are the basis of long-lasting humoral immunity. They respond to re-encountered antigens by rapidly producing specific antibodies and forming germinal centers (GCs), a recall response that has been known for decades but remains poorly understood. We found that the receptor for the cytokine IL-9 (IL-9R) was induced selectively on Bmem cells after primary immunization and that IL-9R-deficient mice exhibited a normal primary antibody response but impaired recall antibody responses, with attenuated population expansion and plasma-cell differentiation of Bmem cells. In contrast, there was augmented GC formation, possibly due to defective downregulation of the ligand for the co-stimulatory receptor ICOS on Bmem cells. A fraction of Bmem cells produced IL-9. These findings indicate that IL-9R signaling in Bmem cells regulates humoral recall responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cell Differentiation
  • Cells, Cultured
  • Germinal Center / physiology*
  • Immunity, Humoral
  • Immunization, Secondary
  • Immunoglobulin Variable Region / genetics
  • Immunologic Memory
  • Inducible T-Cell Co-Stimulator Protein / genetics
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Interleukin-9 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasma Cells / immunology*
  • Receptors, Interleukin-9 / genetics*
  • Receptors, Interleukin-9 / metabolism
  • Signal Transduction

Substances

  • Immunoglobulin Variable Region
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukin-9
  • Receptors, Interleukin-9