In:
Liver International, Wiley, Vol. 38, No. 3 ( 2018-03), p. 542-552
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1478-3223
,
1478-3231
DOI:
10.1111/liv.2018.38.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2124684-1