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

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

Author information

1
Department of Clinical Laboratory, FuXing Hospital, Capital Medical University, Beijing, China.
2
Beijing You An Hospital, Capital Medical University, Beijing, China.
3
Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin, China.
4
BGI-Shenzhen, Shenzhen, China.
5
Tianjin Marvelbio Technology Co. Ltd, Tianjin, China.
6
Geneplus-Beijing, Beijing, China.
7
Prenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Beijing, China.
8
Department of Pathology, McGill University, Montreal, QC, Canada.

Abstract

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

PMID:
28834158
DOI:
10.1111/liv.13554
[Indexed for MEDLINE]

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