Novel role for spleen B cells in inflammatory response to bacterial toxins
Research team identifies a role for spleen marginal zone B lymphocytes in intensifying the inflammatory response to endotoxins through cytokine production
- Date:
- May 9, 2016
- Source:
- University of Tsukuba
- Summary:
- A new role for marginal zone B lymphocytes has been discovered: enhancing inflammatory responses to bacterial lipopolysaccharides. These findings broaden understanding of marginal zone B cell function and interleukin-6 signaling in the immune system, which could be exploited to treat sepsis.
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The inability to adequately respond to infection can cause a whole-body state of inflammation known as sepsis. This can eventually lead to systemic inflammatory response syndrome (SIRS), and even death. White blood cells known as B lymphocytes (B cells) produce antibodies in response to infections such as blood-borne pathogens. B cells of the marginal zone (MZ), which separates circulating blood from spleen lymphoid tissue, contribute to this early immune response, but their role in inflammation has remained unclear.
A research team centered at the University of Tsukuba has now revealed that MZ B cells also produce the signaling proteins cytokines and chemokines involved in inflammatory responses. They recently reported the results of their study in Nature Communications.
Lipopolysaccharides (LPS) are endotoxic products from Gram-negative bacteria that can trigger SIRS. The researchers showed that mice injected with LPS from E. coli were more resistant to endotoxic shock and lived longer if they lacked MZ B cells, suggesting these cells' crucial role in inflammatory response against LPS. MZ B cells were found to produce large quantities of the inflammatory cytokine interleukin (IL)-6, as well as some chemokines, in response to LPS stimulation.
The researchers experimented with blocking the IL-6 function slightly before or a few hours after the LPS injection. "We found that mice were protected against endotoxic shock and survived for longer if IL-6 signaling was stopped at the later stage," lead author Shin-ichiro Honda says. "This is significant in developing treatments for sepsis." After examining the signaling process in greater detail, another protein of the immune system, Toll-like receptor 4 (TLR4), was shown to be necessary for IL-6 production; LPS directly stimulates MZ B cells via TLR4, leading to the production.
Fcα/µR is mainly expressed on lymphoid tissue immune cells, where it acts as a receptor for IgA and IgM antibodies. It is also expressed on MZ B cells, but its role there was unknown. The researchers studied in Fcα/µR-deficient mice and found that their MZ B cells produced much less IL-6 in response to LPS than those of control mice. "We observed that a physical association with Fcα/µR was required for forming the TLR4 complex and IL-6 production in response to LPS," corresponding author Akira Shibuya explains. MZ B cells therefore emerge as a regulator of immune responses with a strong pro-inflammatory role in IL-6 production in endotoxic shock.
Story Source:
Materials provided by University of Tsukuba. Note: Content may be edited for style and length.
Journal Reference:
- Shin-ichiro Honda, Kazuki Sato, Naoya Totsuka, Satoshi Fujiyama, Manabu Fujimoto, Kensuke Miyake, Chigusa Nakahashi-Oda, Satoko Tahara-Hanaoka, Kazuko Shibuya, Akira Shibuya. Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signalling. Nature Communications, 2016; 7: 11498 DOI: 10.1038/ncomms11498
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