Human B cells induce dendritic cell maturation and favour Th2 polarization by inducing OX-40 ligand

Nat Commun. 2014 Jun 9:5:4092. doi: 10.1038/ncomms5092.

Abstract

Dendritic cells (DCs) play a critical role in immune homeostasis by regulating the functions of various immune cells, including T and B cells. Notably, DCs also undergo education on reciprocal signalling by these immune cells and environmental factors. Various reports demonstrated that B cells have profound regulatory functions, although only few reports have explored the regulation of human DCs by B cells. Here we demonstrate that activated but not resting B cells induce maturation of DCs with distinct features to polarize Th2 cells that secrete interleukin (IL)-5, IL-4 and IL-13. B-cell-induced maturation of DCs is contact dependent and implicates signalling of B-cell activation molecules CD69, B-cell-activating factor receptor, and transmembrane activator and calcium-modulating cyclophilin ligand interactor. Mechanistically, differentiation of Th2 cells by B-cell-matured DCs is dependent on OX-40 ligand. Collectively, our results suggest that B cells have the ability to control their own effector functions by enhancing the ability of human DCs to mediate Th2 differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / immunology
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • B-Cell Activation Factor Receptor / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Culture Techniques
  • Cell Differentiation / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Humans
  • Interleukin-13 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Lectins, C-Type / immunology
  • Leukocytes, Mononuclear / immunology
  • OX40 Ligand / immunology*
  • Signal Transduction / immunology*
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Transmembrane Activator and CAML Interactor Protein / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • B-Cell Activation Factor Receptor
  • CD69 antigen
  • IL4 protein, human
  • IL5 protein, human
  • Interleukin-13
  • Interleukin-5
  • Lectins, C-Type
  • OX40 Ligand
  • TNFRSF13B protein, human
  • TNFRSF13C protein, human
  • TNFSF4 protein, human
  • Transmembrane Activator and CAML Interactor Protein
  • Interleukin-4