Investigating the role of FcRL4\(^+\) B cells at the site of epithelial inflammation

Liu, Yuxin ORCID: 0000-0003-2606-5585 (2022). Investigating the role of FcRL4\(^+\) B cells at the site of epithelial inflammation. University of Birmingham. Ph.D.

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Abstract

The slow and progressive deterioration of the small bile ducts is a hallmark of primary biliary cholangitis (PBC). This damage is mediated by infiltrating lymphocytes which form aggregates surrounding the small bile ducts eventually leading to cholestasis and cirrhosis. A subset of memory B cells expressing the surface marker Fc receptor like 4 (FcRL4) have been implicated in the pathogenesis of rheumatoid arthritis and primary Sjogren's syndrome. Here, we addressed the hypothesis that the FcRL4\(^+\) B cells are involved in the lymphoepithelial lesion that leads to the destruction of bile ducts in PBC patients and explored their role in the disease. In explant livers from patients undergoing liver transplantation, FcRL4\(^+\) B cells were identified in PBC livers and were largely absent in other end-stage liver diseases. Within the PBC liver, these cells are highly proliferative and can be seen within immune infiltrates that surround and infiltrate the damaged biliary epithelium. FcRL4\(^+\) B cells isolated from the PBC liver are enriched for CD27\(^+\)IgD\(^-\) class-switched memory cells and CD11c\(^+\)CD21\(^-\)T-bet\(^+\) age associated B cells (ABCs). FcRL4 is a receptor for IgA aggregates. FcRL4\(^+\) B cells isolated from end-stage PBC liver have IgA captured on their surface. In vitro, FcRL4 expressing cells can bind IgA from patient derived bile. High levels of expression of co-stimulatory molecules CD80 and CD86 by FcRL4\(^+\) suggest that they can act as antigen presenting cells. FcRL4\(^+\) B cells preferentially express IgA BCR, suggesting a mucosal origin. Together with their ability to capture IgA immune complexes, these findings suggest that FcRL4\(^+\) B cells may act as a link between mucosal immunity and immune mediated damage of the small bile ducts in PBC.

Type of Work:	Thesis (Doctorates > Ph.D.)
Award Type:	Doctorates > Ph.D.
Supervisor(s):	Supervisor(s) Email ORCID Scheel-Toellner, Dagmar UNSPECIFIED UNSPECIFIED Stamataki, Zania UNSPECIFIED UNSPECIFIED Hirschfield, Gideon UNSPECIFIED UNSPECIFIED Raza, Karim UNSPECIFIED UNSPECIFIED
Licence:	All rights reserved
College/Faculty:	Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department:	Institute of Inflammation and Ageing
Funders:	Wellcome Trust
Subjects:	Q Science > QR Microbiology > QR180 Immunology
URI:	http://etheses.bham.ac.uk/id/eprint/13179

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