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

• Published in: Nature communications Vol. 7; no. 7; pp. 11498 - 10
• Main Authors: 藤本 学, 小田 ちぐさ, 田原 聡子, 渋谷 和子, 渋谷 彰, Honda Shin-ichiro, Sato Kazuki, Totsuka Naoya, Fujiyama Satoshi, Fujimoto Manabu, Miyake Kensuke, Nakahashi-Oda Chigusa, Tahara-Hanaoka Satoko, Shibuya Kazuko, Shibuya Akira
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 05.05.2016; Nature Publishing Group UK; Nature Portfolio
• Subjects: 631/250/1619/40/2507; 631/250/1933; 631/250/256; 631/80/86; 64/60; 96/21; Animals; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Escherichia coli Infections - physiopathology; Humanities and Social Sciences; Interleukin-6 - genetics; Interleukin-6 - metabolism; Lipopolysaccharides - pharmacology; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Myeloid Differentiation Factor 88 - metabolism; NF-kappa B - metabolism; Receptors, Fc - genetics; Receptors, Fc - metabolism; Science; Science (multidisciplinary); Shock, Septic - physiopathology; Signal Transduction - drug effects; Signal Transduction - genetics; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism
• ISSN: 2041-1723; 2041-1723
• 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.