Characterising hepatic B cell subsets in human chronic liver disease

R Medicine > R Medicine (General)

Purswani, Sudha ; Stamataki, Zania,Adams, David

University:University of Birmingham

Department:School of Immunity and Infection

关键词: R Medicine;    R Medicine (General);   

Others  :  http://etheses.bham.ac.uk//id/eprint/7590/1/Purswani17PhD.pdf

来源: University of Birmingham eTheses Repository

【 摘 要 】

B cells have been proven to have a significant role in liver fibrosis. We postulate that enrichment of B cell subsets in hepatic diseases may implicate this population in liver pathogenesis. When comparing total B cells from human immune and non-immune-mediated liver disease explants, we found an enrichment of CD20+ B cells in PBC. Furthermore, phenotypic characterization of 11 B cell subsets in matched liver and blood highlighted an enriched naïve peripheral population, and activated B cell subsets in livers. Newly identified CD19+CD24-CD38- and CD19+CD24-CD38int B cells were also augmented in livers compared to matched blood. Furthermore, CD24-CD38- B cells were elevated in PBC and formed aggregates in tissues, whereas CD24-CD38int B cells localized around bile ducts and along fibrotic tracts in PBC. CD24-CD38int B cells secreted pro-inflammatory (IL-6, IFN-γ) and immunosuppressive (IL-10) cytokines following stimulation with CpG compared to other B cell subsets, implying that CD24- B cells may play a role in liver disease pathogenesis. Our findings suggest that B cells may be influential in hepatic disease progression and pathogenesis. Elucidating their role further could provide possible therapeutic targets for prevention or treatment of chronic liver disease.