Novel Role for Spleen B Cells in Inflammatory Response to Bacterial Toxins
Research team led by the University of Tsukuba identifies a role for spleen marginal zone B lymphocytes
in intensifying the inflammatory response to endotoxins through cytokine production
Tsukuba, Japan – 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 inresponse 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 shockand 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 indeveloping treatments for sepsis.” After examining the signaling process in greater detail, another proteinof 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 inFcα/µR-deficient mice and found that their MZ B cells produced much less IL-6 in response to LPS thanthose of control mice. “We observed that a physical association with Fcα/µR was required for forming theTLR4 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 inIL-6 production in endotoxic shock.
The article, “Marginal zone B cells exacerbate endotoxin shock via interleukin-6 secretion induced byFca/µR-coupled TLR4 signalling” was published in Nature Communications at DOI:
10.1038/ncomms11498
Release Summary Text: University of Tsukuba-led researchers have identified a new role for marginalzone B lymphocytes in enhancing inflammatory responses to bacterial lipopolysaccharides. Marginalzone B cells were shown to produce pro-inflammatory cytokine interleukin-6 in response tolipopolysaccharide stimulation. Interleukin-6 production requires TLR4 signaling in relation to the antibodyreceptor Fcα/µR. 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.
Primary Keywords: Biology
Additional Keywords: Biochemistry, Cell Biology, Molecular Biology, Toxicology

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Image Title: Spleen MZ B cells contribute to inflammatory response against endotoxins
Image Caption: B cells from the marginal zone (MZ) of the spleen produce high levels of the proinflammatory cytokine interleukin-6 (IL-6) in response to bacterial endotoxins. This response iscoordinated by a signaling reaction involving TLR4 and Fcα/µR, and leads to systemic inflammation andendotoxic shock.