title: Hepatic B cells are readily activated by Toll-like receptor-4 ligation and secrete less interleukin-10 than lymphoid tissue B cells.
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.
authors.affiliation: Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: D B
authors.initials: DB
authors.lastname: Stolz
authors.forename: G
authors.initials: G
authors.lastname: Chalasani
authors.forename: A W
authors.initials: AW
authors.lastname: Thomson
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000276:immunology* / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: B cells; IL-10; TLR-4; dendritic cells; liver