Clonal characteristics of paired infiltrating and circulating B lymphocyte repertoire in patients with primary biliary cholangitis

Liver Int. 2018 Mar;38(3):542-552. doi: 10.1111/liv.13554. Epub 2017 Sep 19.


Background: PBC is a prototypical autoimmune liver disease characterized by portal lymphoplasmacyte infiltration. ALD is a prototypical environment-driven disease, featured by mild lymphocyte infiltration. We hypothesize that B cells are more involved in the pathogenesis of PBC. By analysing the infiltrating B cell repertoire, we aimed to unveil greater oligoclonal expansion and active clonal exchange between liver and periphery in PBC than in ALD patients.

Methods: Using NGS of Ig H chain genes, we analysed the liver-infiltrating and paired peripheral B lymphocyte repertoire from nine PBC and four ALD patients.

Results: In the liver of PBC and ALD patients, (i) roughly 10% of the B lymphocytes were clonally related and highly expressed, and there were also lineages that underwent extensive clonal expansion; (ii) there was different use of IGHV/IGHJ segments between PBC and ALD, suggesting distinct Ag exposure backgrounds, but this did not lead to a significant difference in their clonal expansion level. Analysis of data sets from paired samples further revealed, (iii) direct clonal exchange and evolutionally related B cell clones between the infiltrating and peripheral repertoire; (iv) the seeding of the infiltrating clones to periphery, and peripheral ones to the liver, for further extensive evolution.

Conclusions: The oligoclonally expanded nature of the infiltrating B cell repertoire implies B cell immunity is involved in the pathogenesis of both diseases. The observed clonal exchange might provide an approach to identify and monitor the infiltrating B cells through the periphery.

Keywords: Ig repertoire; Primary biliary cholangitis; clonal exchange; oligoclonal expansion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Clone Cells
  • Female
  • Genes, Immunoglobulin
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Liver / pathology*
  • Liver Cirrhosis, Biliary / immunology*
  • Male
  • Middle Aged