FcγRIIb attenuates TLR4‑mediated NF‑κB signaling in B cells

Mol Med Rep. 2017 Oct;16(4):5693-5698. doi: 10.3892/mmr.2017.7269. Epub 2017 Aug 17.

Abstract

Toll‑like receptors (TLRs) serve a vital role in activating the innate immune system by sensing conserved microbial products. Fc γ receptor IIb (FcγRIIb), the inhibitory Fc receptor, exerts its immune regulatory functions by binding to the immunoglobulin G Fc domain. Although the individual roles of TLRs and FcγRIIb have been studied intensively, the cross‑talk between FcγRIIb and TLR4 on B cells remains unknown. The present study demonstrated that FcγRIIb ligation by the immune complex (IC) attenuated the TLR4‑triggered nuclear factor (NF)‑κΒ activation, and decreased the release of interleukin (IL)‑6 from B cells, via enhancing LYN proto‑oncogene (Lyn) phosphorylation. In addition, IC treatment protected mice from lethal endotoxic shock. Accordingly, IC decreased the LPS‑induced serum levels of IL‑6, as well as intracellular IL‑6 production in B cells in vivo. However, these protective and inhibitory effects of IC were not observed in FcγRIIb‑/‑ mice. In conclusion, the present data demonstrated that FcγRIIb inhibited TLR4 signaling in B cells by activating Lyn phosphorylation and by inhibiting NF‑κΒ signaling. The present study elucidated the mechanism associated with the TLR4 and FcγRIIb cross‑talk in B cells.

MeSH terms

  • Animals
  • Antigen-Antibody Complex / adverse effects
  • Antigen-Antibody Complex / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Cytokines / metabolism
  • Inflammation Mediators
  • Lipopolysaccharides / adverse effects
  • Lipopolysaccharides / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Knockout
  • NF-kappa B / metabolism*
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism*
  • Shock, Septic / etiology
  • Shock, Septic / metabolism
  • Shock, Septic / pathology
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Antigen-Antibody Complex
  • Cytokines
  • Fc gamma receptor IIB
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Receptors, IgG
  • Toll-Like Receptor 4