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

NATURE COMMUNICATIONS | ARTICLE OPEN

Shin-ichiro Honda,

Kazuki Sato,

Naoya Totsuka,

Satoshi Fujiyama,

Manabu Fujimoto,

Kensuke Miyake,

Chigusa Nakahashi-Oda,

Satoko Tahara-Hanaoka,

Kazuko Shibuya

& Akira Shibuya

• Affiliations
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• Corresponding author

Nature Communications

 

7,

 

Article number:

 

11498

 

doi:10.1038/ncomms11498

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Abstract

• Abstract• 
• Introduction• 
• Results• 
• Discussion• 
• Methods• 
• Additional information• 
• References•
• Acknowledgements• 
• Author information• 
• Supplementary information

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.