Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signalling

Nat Commun. 2016 May 5;7:11498. doi: 10.1038/ncomms11498.


Marginal zone (MZ) B cells produce a first wave of antibodies for protection from blood-borne pathogens. However, the role of MZ B cells in inflammatory responses has not been elucidated. Here we show that MZ B cells produce pro-inflammatory cytokines, such as interleukin-6 (IL-6), and exacerbate systemic inflammatory responses to lipopolysaccharide (LPS). After intravenous injection of LPS or E. coli, mice deficient in MZ B cells or IL-6 only in MZ B cells have attenuated systemic inflammatory responses and prolonged survival compared with wild-type mice. LPS directly stimulates MZ B cells via Toll-like receptor 4 (TLR4) and MyD88 pathways for IL-6 production. Furthermore, TLR4 requires physical and functional association with Fcα/μR (CD351) for its oligomer formation, NF-κB signalling and IL-6 production from MZ B cells; this association is responsible for systemic inflammatory responses and endotoxic shock. These results reveal a pro-inflammatory role of MZ B cells in endotoxic shock.

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism*
  • Escherichia coli Infections / physiopathology
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Lipopolysaccharides / pharmacology
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / metabolism
  • Receptors, Fc / genetics
  • Receptors, Fc / metabolism*
  • Shock, Septic / physiopathology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*


  • Fcalpha-mu protein, mouse
  • Interleukin-6
  • Lipopolysaccharides
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Receptors, Fc
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4