Clonal characteristics of paired infiltrating and circulating B lymphocyte repertoire in patients with primary biliary cholangitis
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 infi...
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Veröffentlicht in: | Liver international 2018-03, Vol.38 (3), p.542-552 |
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creator | Tan, Yan‐guo Wang, Xiao‐feng Zhang, Ming Yan, Hui‐ping Lin, Dong‐dong Wang, Yu‐qi Zhang, Hai‐ping Yu, Xin‐qiu Liao, Hui‐yu Wang, Yi‐peng Lv, Fu‐dong Gao, Zu‐hua |
description | 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. |
doi_str_mv | 10.1111/liv.13554 |
format | Article |
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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.</description><identifier>ISSN: 1478-3223</identifier><identifier>EISSN: 1478-3231</identifier><identifier>DOI: 10.1111/liv.13554</identifier><identifier>PMID: 28834158</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; B-Lymphocytes - cytology ; B-Lymphocytes - immunology ; Cholangitis ; clonal exchange ; Clone Cells ; Data processing ; Exchanging ; Expansion ; Female ; Genes, Immunoglobulin ; High-Throughput Nucleotide Sequencing ; Humans ; Ig repertoire ; Immunity ; Immunoglobulins ; Infiltration ; Liver ; Liver - pathology ; Liver Cirrhosis, Biliary - immunology ; Liver diseases ; Lymphocyte receptors ; Lymphocytes ; Lymphocytes B ; Male ; Middle Aged ; oligoclonal expansion ; Pathogenesis ; Patients ; Primary biliary cholangitis ; T cell receptors</subject><ispartof>Liver international, 2018-03, Vol.38 (3), p.542-552</ispartof><rights>2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>2018 John Wiley & Sons A/S</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3534-50d1b5df20c1168f24ebaf5acdb88683987f30b04eb27d0600e1a69f12cc820e3</citedby><cites>FETCH-LOGICAL-c3534-50d1b5df20c1168f24ebaf5acdb88683987f30b04eb27d0600e1a69f12cc820e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fliv.13554$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fliv.13554$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28834158$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tan, Yan‐guo</creatorcontrib><creatorcontrib>Wang, Xiao‐feng</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Yan, Hui‐ping</creatorcontrib><creatorcontrib>Lin, Dong‐dong</creatorcontrib><creatorcontrib>Wang, Yu‐qi</creatorcontrib><creatorcontrib>Zhang, Hai‐ping</creatorcontrib><creatorcontrib>Yu, Xin‐qiu</creatorcontrib><creatorcontrib>Liao, Hui‐yu</creatorcontrib><creatorcontrib>Wang, Yi‐peng</creatorcontrib><creatorcontrib>Lv, Fu‐dong</creatorcontrib><creatorcontrib>Gao, Zu‐hua</creatorcontrib><title>Clonal characteristics of paired infiltrating and circulating B lymphocyte repertoire in patients with primary biliary cholangitis</title><title>Liver international</title><addtitle>Liver Int</addtitle><description>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.</description><subject>Adult</subject><subject>B-Lymphocytes - cytology</subject><subject>B-Lymphocytes - immunology</subject><subject>Cholangitis</subject><subject>clonal exchange</subject><subject>Clone Cells</subject><subject>Data processing</subject><subject>Exchanging</subject><subject>Expansion</subject><subject>Female</subject><subject>Genes, Immunoglobulin</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Ig repertoire</subject><subject>Immunity</subject><subject>Immunoglobulins</subject><subject>Infiltration</subject><subject>Liver</subject><subject>Liver - pathology</subject><subject>Liver Cirrhosis, Biliary - immunology</subject><subject>Liver diseases</subject><subject>Lymphocyte receptors</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Male</subject><subject>Middle Aged</subject><subject>oligoclonal expansion</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Primary biliary cholangitis</subject><subject>T cell receptors</subject><issn>1478-3223</issn><issn>1478-3231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU-PFCEQxYnRuOvqwS9gSLzoYXYpaLrpo078s8kkXtQroWnYqQ3TtEC7maufXNYe92BiXaogv_dS8Ah5CewSal0F_HkJQsrmETmHplMbwQU8fpi5OCPPcr5lDPpewlNyxpUSDUh1Tn5tQ5xMoHZvkrHFJcwFbabR09lgciPFyWMoyRScbqiZRmox2SWs5_c0HA_zPtpjcTS52aUSq6qKqrygm0qmd1j2dE54MOlIBwx43-0-BjPdYMH8nDzxJmT34tQvyLePH75uP292Xz5db9_tNlZI0WwkG2GQo-fMArTK88YNxktjx0GpVoledV6wgdVr3o2sZcyBaXsP3FrFmRMX5M3qO6f4Y3G56ANm60Ldw8Ula-gFh7YD4BV9_Q96G5dU_ylrzljHml7KvlJvV8qmmHNyXp9eqYHp-2B0DUb_Caayr06Oy3Bw4wP5N4kKXK3AHQZ3_L-T3l1_Xy1_A7nhmfE</recordid><startdate>201803</startdate><enddate>201803</enddate><creator>Tan, Yan‐guo</creator><creator>Wang, Xiao‐feng</creator><creator>Zhang, Ming</creator><creator>Yan, Hui‐ping</creator><creator>Lin, Dong‐dong</creator><creator>Wang, Yu‐qi</creator><creator>Zhang, Hai‐ping</creator><creator>Yu, Xin‐qiu</creator><creator>Liao, Hui‐yu</creator><creator>Wang, Yi‐peng</creator><creator>Lv, Fu‐dong</creator><creator>Gao, Zu‐hua</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201803</creationdate><title>Clonal characteristics of paired infiltrating and circulating B lymphocyte repertoire in patients with primary biliary cholangitis</title><author>Tan, Yan‐guo ; Wang, Xiao‐feng ; Zhang, Ming ; Yan, Hui‐ping ; Lin, Dong‐dong ; Wang, Yu‐qi ; Zhang, Hai‐ping ; Yu, Xin‐qiu ; Liao, Hui‐yu ; Wang, Yi‐peng ; Lv, Fu‐dong ; Gao, Zu‐hua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3534-50d1b5df20c1168f24ebaf5acdb88683987f30b04eb27d0600e1a69f12cc820e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>B-Lymphocytes - cytology</topic><topic>B-Lymphocytes - immunology</topic><topic>Cholangitis</topic><topic>clonal exchange</topic><topic>Clone Cells</topic><topic>Data processing</topic><topic>Exchanging</topic><topic>Expansion</topic><topic>Female</topic><topic>Genes, Immunoglobulin</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>Ig repertoire</topic><topic>Immunity</topic><topic>Immunoglobulins</topic><topic>Infiltration</topic><topic>Liver</topic><topic>Liver - pathology</topic><topic>Liver Cirrhosis, Biliary - immunology</topic><topic>Liver diseases</topic><topic>Lymphocyte receptors</topic><topic>Lymphocytes</topic><topic>Lymphocytes B</topic><topic>Male</topic><topic>Middle Aged</topic><topic>oligoclonal expansion</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Primary biliary cholangitis</topic><topic>T cell receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tan, Yan‐guo</creatorcontrib><creatorcontrib>Wang, Xiao‐feng</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Yan, Hui‐ping</creatorcontrib><creatorcontrib>Lin, Dong‐dong</creatorcontrib><creatorcontrib>Wang, Yu‐qi</creatorcontrib><creatorcontrib>Zhang, Hai‐ping</creatorcontrib><creatorcontrib>Yu, Xin‐qiu</creatorcontrib><creatorcontrib>Liao, Hui‐yu</creatorcontrib><creatorcontrib>Wang, Yi‐peng</creatorcontrib><creatorcontrib>Lv, Fu‐dong</creatorcontrib><creatorcontrib>Gao, Zu‐hua</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Liver international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tan, Yan‐guo</au><au>Wang, Xiao‐feng</au><au>Zhang, Ming</au><au>Yan, Hui‐ping</au><au>Lin, Dong‐dong</au><au>Wang, Yu‐qi</au><au>Zhang, Hai‐ping</au><au>Yu, Xin‐qiu</au><au>Liao, Hui‐yu</au><au>Wang, Yi‐peng</au><au>Lv, Fu‐dong</au><au>Gao, Zu‐hua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clonal characteristics of paired infiltrating and circulating B lymphocyte repertoire in patients with primary biliary cholangitis</atitle><jtitle>Liver international</jtitle><addtitle>Liver Int</addtitle><date>2018-03</date><risdate>2018</risdate><volume>38</volume><issue>3</issue><spage>542</spage><epage>552</epage><pages>542-552</pages><issn>1478-3223</issn><eissn>1478-3231</eissn><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.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28834158</pmid><doi>10.1111/liv.13554</doi><tpages>11</tpages></addata></record> |
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subjects | Adult B-Lymphocytes - cytology B-Lymphocytes - immunology Cholangitis clonal exchange Clone Cells Data processing Exchanging Expansion Female Genes, Immunoglobulin High-Throughput Nucleotide Sequencing Humans Ig repertoire Immunity Immunoglobulins Infiltration Liver Liver - pathology Liver Cirrhosis, Biliary - immunology Liver diseases Lymphocyte receptors Lymphocytes Lymphocytes B Male Middle Aged oligoclonal expansion Pathogenesis Patients Primary biliary cholangitis T cell receptors |
title | Clonal characteristics of paired infiltrating and circulating B lymphocyte repertoire in patients with primary biliary cholangitis |
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