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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:715716 |
| Date | January 2017 |
| Creators | Purswani, Sudha |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/7590/ |
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