A novel proangiogenic B cell subset is increased in cancer and chronic inflammation

B cells contribute to immune responses through the production of immunoglobulins, antigen presentation, and cytokine production. Several B cell subsets with distinct functions and polarized cytokine profiles have been reported. In this study, we used transcriptomics analysis of immortalized B cell c...

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Veröffentlicht in:	Science advances 2020-05, Vol.6 (20), p.eaaz3559-eaaz3559
Hauptverfasser:	van de Veen, Willem, Globinska, Anna, Jansen, Kirstin, Straumann, Alex, Kubo, Terufumi, Verschoor, Daniëlle, Wirz, Oliver F, Castro-Giner, Francesc, Tan, Ge, Rückert, Beate, Ochsner, Urs, Herrmann, Marietta, Stanić, Barbara, van Splunter, Marloes, Huntjens, Daan, Wallimann, Alexandra, Fonseca Guevara, Rodney J, Spits, Hergen, Ignatova, Desislava, Chang, Yun-Tsan, Fassnacht, Christina, Guenova, Emmanuella, Flatz, Lukas, Akdis, Cezmi A, Akdis, Mübeccel
Format:	Artikel
Sprache:	eng
Schlagworte:	B-Lymphocyte Subsets - metabolism Cancer Cytokines - metabolism Eosinophilic Esophagitis Humans Immunoglobulin G Inflammation Integrin alpha2 Melanoma - genetics SciAdv r-articles
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creator	van de Veen, Willem Globinska, Anna Jansen, Kirstin Straumann, Alex Kubo, Terufumi Verschoor, Daniëlle Wirz, Oliver F Castro-Giner, Francesc Tan, Ge Rückert, Beate Ochsner, Urs Herrmann, Marietta Stanić, Barbara van Splunter, Marloes Huntjens, Daan Wallimann, Alexandra Fonseca Guevara, Rodney J Spits, Hergen Ignatova, Desislava Chang, Yun-Tsan Fassnacht, Christina Guenova, Emmanuella Flatz, Lukas Akdis, Cezmi A Akdis, Mübeccel
description	B cells contribute to immune responses through the production of immunoglobulins, antigen presentation, and cytokine production. Several B cell subsets with distinct functions and polarized cytokine profiles have been reported. In this study, we used transcriptomics analysis of immortalized B cell clones to identify an IgG4 B cell subset with a unique function. These B cells are characterized by simultaneous expression of proangiogenic cytokines including VEGF, CYR61, ADM, FGF2, PDGFA, and MDK. Consequently, supernatants from these clones efficiently promote endothelial cell tube formation. We identified CD49b and CD73 as surface markers identifying proangiogenic B cells. Circulating CD49b CD73 B cells showed significantly increased frequency in patients with melanoma and eosinophilic esophagitis (EoE), two diseases associated with angiogenesis. In addition, tissue-infiltrating IgG4 CD49b CD73 B cells expressing proangiogenic cytokines were detected in patients with EoE and melanoma. Our results demonstrate a previously unidentified proangiogenic B cell subset characterized by expression of CD49b, CD73, and proangiogenic cytokines.
doi_str_mv	10.1126/sciadv.aaz3559
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Several B cell subsets with distinct functions and polarized cytokine profiles have been reported. In this study, we used transcriptomics analysis of immortalized B cell clones to identify an IgG4 B cell subset with a unique function. These B cells are characterized by simultaneous expression of proangiogenic cytokines including VEGF, CYR61, ADM, FGF2, PDGFA, and MDK. Consequently, supernatants from these clones efficiently promote endothelial cell tube formation. We identified CD49b and CD73 as surface markers identifying proangiogenic B cells. Circulating CD49b CD73 B cells showed significantly increased frequency in patients with melanoma and eosinophilic esophagitis (EoE), two diseases associated with angiogenesis. In addition, tissue-infiltrating IgG4 CD49b CD73 B cells expressing proangiogenic cytokines were detected in patients with EoE and melanoma. 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Our results demonstrate a previously unidentified proangiogenic B cell subset characterized by expression of CD49b, CD73, and proangiogenic cytokines.</description><subject>B-Lymphocyte Subsets - metabolism</subject><subject>Cancer</subject><subject>Cytokines - metabolism</subject><subject>Eosinophilic Esophagitis</subject><subject>Humans</subject><subject>Immunoglobulin G</subject><subject>Inflammation</subject><subject>Integrin alpha2</subject><subject>Melanoma - genetics</subject><subject>SciAdv r-articles</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1LAzEQDaJoqb16lBy9tOZ7zUWoxS8oeFDPIZudbSO7SU22Bf31bmktOpcZmDdv5s1D6IKSCaVMXWfnbbWZWPvNpdRHaMB4IcdMipvjP_UZGuX8QQihQilJ9Sk640wwJXQxQK9THOIGGrxK0YaFjwsI3uE77KBpcF6XGTrsM_bBJbAZqr7CzgYHCdtQYbdMcTvgQ93YtrWdj-EcndS2yTDa5yF6f7h_mz2N5y-Pz7PpfOy4Jt0YuFJQcV6KsgCqma5dH5STkmoButCyYKq0JVGFFFLaGhRlmhRQKi16BXyIbne8q3XZQuUgdMk2ZpV8a9OXidab_53gl2YRN6ZgjHAie4KrPUGKn2vInWl93gq3AeI6GyaIUILd9OghmuygLsWcE9SHNZSYrRlmZ4bZm9EPXP497gD_fT3_AYZkiCg</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>van de Veen, Willem</creator><creator>Globinska, Anna</creator><creator>Jansen, Kirstin</creator><creator>Straumann, Alex</creator><creator>Kubo, Terufumi</creator><creator>Verschoor, Daniëlle</creator><creator>Wirz, Oliver F</creator><creator>Castro-Giner, Francesc</creator><creator>Tan, Ge</creator><creator>Rückert, Beate</creator><creator>Ochsner, Urs</creator><creator>Herrmann, Marietta</creator><creator>Stanić, Barbara</creator><creator>van Splunter, Marloes</creator><creator>Huntjens, Daan</creator><creator>Wallimann, Alexandra</creator><creator>Fonseca Guevara, Rodney J</creator><creator>Spits, Hergen</creator><creator>Ignatova, Desislava</creator><creator>Chang, Yun-Tsan</creator><creator>Fassnacht, Christina</creator><creator>Guenova, Emmanuella</creator><creator>Flatz, Lukas</creator><creator>Akdis, Cezmi A</creator><creator>Akdis, Mübeccel</creator><general>American Association for the Advancement of Science</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3269-8338</orcidid><orcidid>https://orcid.org/0000-0003-0554-9943</orcidid><orcidid>https://orcid.org/0000-0001-5379-2687</orcidid><orcidid>https://orcid.org/0000-0002-2412-7474</orcidid><orcidid>https://orcid.org/0000-0001-5478-8735</orcidid><orcidid>https://orcid.org/0000-0001-9274-2551</orcidid><orcidid>https://orcid.org/0000-0001-6111-0754</orcidid><orcidid>https://orcid.org/0000-0001-5354-9935</orcidid><orcidid>https://orcid.org/0000-0001-8020-019X</orcidid><orcidid>https://orcid.org/0000-0001-9951-6688</orcidid><orcidid>https://orcid.org/0000-0003-0377-6464</orcidid><orcidid>https://orcid.org/0000-0003-0026-8739</orcidid><orcidid>https://orcid.org/0000-0001-9683-8390</orcidid><orcidid>https://orcid.org/0000-0002-8695-9030</orcidid></search><sort><creationdate>20200501</creationdate><title>A novel proangiogenic B cell subset is increased in cancer and chronic inflammation</title><author>van de Veen, Willem ; 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subjects	B-Lymphocyte Subsets - metabolism Cancer Cytokines - metabolism Eosinophilic Esophagitis Humans Immunoglobulin G Inflammation Integrin alpha2 Melanoma - genetics SciAdv r-articles
title	A novel proangiogenic B cell subset is increased in cancer and chronic inflammation
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