Prominent role for plasmacytoid dendritic cells in mucosal T cell-independent IgA induction

Immunity. 2011 Feb 25;34(2):247-57. doi: 10.1016/j.immuni.2011.02.002. Epub 2011 Feb 17.

Abstract

Although both conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) are present in the gut-associated lymphoid tissues (GALT), the roles of pDCs in the gut remain largely unknown. Here we show a critical role for pDCs in T cell-independent (TI) IgA production by B cells in the GALT. When pDCs of the mesenteric lymph nodes (MLNs) and Peyer's patches (PPs) (which are representative GALT) were cultured with naive B cells to induce TI IgA class switch recombination (CSR), IgA production was substantially higher than in cocultures of these cells with cDCs. IgA production was dependent on APRIL and BAFF production by pDCs. Importantly, pDC expression of APRIL and BAFF was dependent on stromal cell-derived type I IFN signaling under steady-state conditions. Our findings provide insight into the molecular basis of pDC conditioning to induce mucosal TI IgA production, which may lead to improvements in vaccination strategies and treatment for mucosal-related disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • B-Cell Activating Factor / physiology
  • Coculture Techniques
  • Cytokines / physiology
  • Dendritic Cells / immunology*
  • Germ-Free Life
  • Immunity, Mucosal / immunology*
  • Immunoglobulin A, Secretory / biosynthesis*
  • Immunoglobulin A, Secretory / genetics
  • Immunoglobulin Class Switching*
  • Interferon Type I / physiology
  • Lymph Nodes / immunology
  • Mesentery / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peyer's Patches / immunology
  • Receptor Cross-Talk
  • Receptors, Antigen, T-Cell, alpha-beta / deficiency
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / deficiency
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Stromal Cells / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / physiology

Substances

  • B-Cell Activating Factor
  • Cytokines
  • Immunoglobulin A, Secretory
  • Interferon Type I
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tnfsf13 protein, mouse
  • Tnfsf13b protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 13