Hepatic B cells are readily activated by Toll‐like receptor‐4 ligation and secrete less interleukin‐10 than lymphoid tissue B cells |
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Authors: | H. Zhang D. B. Stolz G. Chalasani A. W. Thomson |
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Affiliation: | 1. Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, , Pittsburgh, PA, USA;2. Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, , Pittsburgh, PA, USA;3. Department of Medicine, University of Pittsburgh School of Medicine, , Pittsburgh, PA, USA;4. Department of Immunology, University of Pittsburgh School of Medicine, , Pittsburgh, PA, USA |
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Abstract: | B cells perform various immunological functions that include production of antibody, presentation of antigens, secretion of multiple cytokines and regulation of immune responses mainly via their secretion of interleukin (IL)‐10. While the liver is regarded both as an important immune organ and a tolerogenic environment, little is known about the functional biology of hepatic B cells. In this study we demonstrate that, following lipopolysaccharide (LPS) stimulation in vivo, normal mouse hepatic B cells rapidly increase their surface expression of CD39, CD40, CD80 and CD86, and produce significantly elevated levels of proinflammatory interferon (IFN)‐γ, IL‐6 and tumour necrosis factor (TNF)‐α compared with splenic B cells. Moreover, LPS‐activated hepatic B cells produce very low levels of IL‐10 compared with activated splenic B cells that produce comparatively high levels of this immunosuppressive cytokine. Splenic, but not hepatic, B cells inhibited the activation of liver conventional myeloid dendritic cells (mDCs). Furthermore, compared with the spleen, the liver exhibited significantly smaller proportions of B1a and marginal zone‐like B cells, which have been shown to produce IL‐10 upon LPS stimulation. These data suggest that, unlike in the spleen, IL‐10‐producing regulatory B cells in the liver are not a prominent cell type. Consistent with this, when compared with liver conventional mDCs from B cell‐deficient mice, those from B cell‐competent wild‐type mice displayed enhanced expression of the cell surface co‐stimulatory molecule CD86, greater production of proinflammatory cytokines (IFN‐γ, IL‐6, IL‐12p40) and reduced secretion of IL‐10. These findings suggest that hepatic B cells have the potential to initiate rather than regulate inflammatory responses. |
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Keywords: | B cells dendritic cells IL‐10 liver TLR‐4 |
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