BCL6 controls contact-dependent help delivery during follicular T-B cell interactions
BCL6 is required for development of follicular T helper (Tfh) cells to support germinal center (GC) formation. However, it is not clear what unique functions programmed by BCL6 can explain its absolute essentiality in T cells for GC formation. We found that ablation of one Bcl6 allele did not apprec...
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Veröffentlicht in: | Immunity (Cambridge, Mass.) Mass.), 2021-10, Vol.54 (10), p.2245-2255.e4 |
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creator | Liu, Dan Yan, Jiacong Sun, Jiahui Liu, Bo Ma, Weiwei Li, Ye Shao, Xingxing Qi, Hai |
description | BCL6 is required for development of follicular T helper (Tfh) cells to support germinal center (GC) formation. However, it is not clear what unique functions programmed by BCL6 can explain its absolute essentiality in T cells for GC formation. We found that ablation of one Bcl6 allele did not appreciably alter early T cell activation and follicular localization but inhibited GC formation and Tfh cell maintenance. BCL6 impinged on Tfh calcium signaling and also controlled Tfh entanglement with and CD40L delivery to B cells. Amounts of BCL6 protein and nominal frequencies of Tfh cells markedly changed within hours after strengths of T-B cell interactions were altered in vivo, while CD40L overexpression rectified both defective GC formation and Tfh cell maintenance because of the BCL6 haploinsufficiency. Our results reveal BCL6 functions in Tfh cells that are essential for GC formation and suggest that BCL6 helps maintain Tfh cell phenotypes in a T cell non-autonomous manner.
•Both copies of Bcl6 gene are required for efficient follicular T-B cell entanglement•BCL6 is required for calcium signaling in Tfh cells and CD40L delivery to B cells•Expression of Tfh markers responds to acute perturbation of T-B cell interactions•Defective functions of BCL6-insufficient T cells are rescued by CD40L overexpression
BCL6 is required for Tfh cell development. Liu et al. show that BCL6 controls calcium signaling of Tfh cells, follicular T-B cell entanglement, and efficient T cell-to-B cell CD40L delivery and promotes Tfh cell maintenance partly in a T cell non-autonomous manner. |
doi_str_mv | 10.1016/j.immuni.2021.08.003 |
format | Article |
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•Both copies of Bcl6 gene are required for efficient follicular T-B cell entanglement•BCL6 is required for calcium signaling in Tfh cells and CD40L delivery to B cells•Expression of Tfh markers responds to acute perturbation of T-B cell interactions•Defective functions of BCL6-insufficient T cells are rescued by CD40L overexpression
BCL6 is required for Tfh cell development. Liu et al. show that BCL6 controls calcium signaling of Tfh cells, follicular T-B cell entanglement, and efficient T cell-to-B cell CD40L delivery and promotes Tfh cell maintenance partly in a T cell non-autonomous manner.</description><identifier>ISSN: 1074-7613</identifier><identifier>EISSN: 1097-4180</identifier><identifier>DOI: 10.1016/j.immuni.2021.08.003</identifier><identifier>PMID: 34464595</identifier><language>eng</language><publisher>Elsevier Inc</publisher><subject>BCL6 ; calcium signaling ; CD40L ; follicle ; germinal center ; intravital imaging ; lymph node ; stim1 ; T-B interactions ; Tfh cells</subject><ispartof>Immunity (Cambridge, Mass.), 2021-10, Vol.54 (10), p.2245-2255.e4</ispartof><rights>2021 The Author(s)</rights><rights>2021 The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-88155f39f40e211f64537faf2801b94b4f9768b674db4e48084007db3e53762b3</citedby><cites>FETCH-LOGICAL-c440t-88155f39f40e211f64537faf2801b94b4f9768b674db4e48084007db3e53762b3</cites><orcidid>0000-0002-9596-7307 ; 0000-0001-5475-3989</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1074761321003332$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids></links><search><creatorcontrib>Liu, Dan</creatorcontrib><creatorcontrib>Yan, Jiacong</creatorcontrib><creatorcontrib>Sun, Jiahui</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Ma, Weiwei</creatorcontrib><creatorcontrib>Li, Ye</creatorcontrib><creatorcontrib>Shao, Xingxing</creatorcontrib><creatorcontrib>Qi, Hai</creatorcontrib><title>BCL6 controls contact-dependent help delivery during follicular T-B cell interactions</title><title>Immunity (Cambridge, Mass.)</title><description>BCL6 is required for development of follicular T helper (Tfh) cells to support germinal center (GC) formation. However, it is not clear what unique functions programmed by BCL6 can explain its absolute essentiality in T cells for GC formation. We found that ablation of one Bcl6 allele did not appreciably alter early T cell activation and follicular localization but inhibited GC formation and Tfh cell maintenance. BCL6 impinged on Tfh calcium signaling and also controlled Tfh entanglement with and CD40L delivery to B cells. Amounts of BCL6 protein and nominal frequencies of Tfh cells markedly changed within hours after strengths of T-B cell interactions were altered in vivo, while CD40L overexpression rectified both defective GC formation and Tfh cell maintenance because of the BCL6 haploinsufficiency. Our results reveal BCL6 functions in Tfh cells that are essential for GC formation and suggest that BCL6 helps maintain Tfh cell phenotypes in a T cell non-autonomous manner.
•Both copies of Bcl6 gene are required for efficient follicular T-B cell entanglement•BCL6 is required for calcium signaling in Tfh cells and CD40L delivery to B cells•Expression of Tfh markers responds to acute perturbation of T-B cell interactions•Defective functions of BCL6-insufficient T cells are rescued by CD40L overexpression
BCL6 is required for Tfh cell development. Liu et al. show that BCL6 controls calcium signaling of Tfh cells, follicular T-B cell entanglement, and efficient T cell-to-B cell CD40L delivery and promotes Tfh cell maintenance partly in a T cell non-autonomous manner.</description><subject>BCL6</subject><subject>calcium signaling</subject><subject>CD40L</subject><subject>follicle</subject><subject>germinal center</subject><subject>intravital imaging</subject><subject>lymph node</subject><subject>stim1</subject><subject>T-B interactions</subject><subject>Tfh cells</subject><issn>1074-7613</issn><issn>1097-4180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kc1O3DAUhS1UBBR4AxZZdpNw7TiJs0EqI34qjdQNrK3EvgaPHHtqJyPx9ngYVNRNVz6Sz_3usQ8hVxQqCrS93lR2mhZvKwaMViAqgPqInFHou5JTAd_2uuNl19L6lHxPaQNAedPDCTmtOW-zbM7I8-1q3RYq-DkGlz7EoOZS4xa9Rj8Xr-i2hUZndxjfCr1E618KE5yzanFDLJ7K20Khc4X1M8Y8a4NPF-TYDC7h5ed5Tp7v755Wj-X698Ov1c91qTiHuRSCNo2pe8MBGaUmZ6o7MxgmgI49H7npu1aMbcf1yJELEByg02ON2deysT4nNwfudhkn1CoHjoOT22inIb7JMFj57423r_Il7KRoWGaxDPjxCYjhz4JplpNN--cMHsOSJGtawXjPmy5b-cGqYkgpovm7hoLcNyI38tCI3DciQcjcyFdEzP-wsxhlUha9Qm0jqlnqYP8PeAcdTJV8</recordid><startdate>20211012</startdate><enddate>20211012</enddate><creator>Liu, Dan</creator><creator>Yan, Jiacong</creator><creator>Sun, Jiahui</creator><creator>Liu, Bo</creator><creator>Ma, Weiwei</creator><creator>Li, Ye</creator><creator>Shao, Xingxing</creator><creator>Qi, Hai</creator><general>Elsevier Inc</general><general>Cell Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9596-7307</orcidid><orcidid>https://orcid.org/0000-0001-5475-3989</orcidid></search><sort><creationdate>20211012</creationdate><title>BCL6 controls contact-dependent help delivery during follicular T-B cell interactions</title><author>Liu, Dan ; Yan, Jiacong ; Sun, Jiahui ; Liu, Bo ; Ma, Weiwei ; Li, Ye ; Shao, Xingxing ; Qi, Hai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-88155f39f40e211f64537faf2801b94b4f9768b674db4e48084007db3e53762b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>BCL6</topic><topic>calcium signaling</topic><topic>CD40L</topic><topic>follicle</topic><topic>germinal center</topic><topic>intravital imaging</topic><topic>lymph node</topic><topic>stim1</topic><topic>T-B interactions</topic><topic>Tfh cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Dan</creatorcontrib><creatorcontrib>Yan, Jiacong</creatorcontrib><creatorcontrib>Sun, Jiahui</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Ma, Weiwei</creatorcontrib><creatorcontrib>Li, Ye</creatorcontrib><creatorcontrib>Shao, Xingxing</creatorcontrib><creatorcontrib>Qi, Hai</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Immunity (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Dan</au><au>Yan, Jiacong</au><au>Sun, Jiahui</au><au>Liu, Bo</au><au>Ma, Weiwei</au><au>Li, Ye</au><au>Shao, Xingxing</au><au>Qi, Hai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BCL6 controls contact-dependent help delivery during follicular T-B cell interactions</atitle><jtitle>Immunity (Cambridge, Mass.)</jtitle><date>2021-10-12</date><risdate>2021</risdate><volume>54</volume><issue>10</issue><spage>2245</spage><epage>2255.e4</epage><pages>2245-2255.e4</pages><issn>1074-7613</issn><eissn>1097-4180</eissn><abstract>BCL6 is required for development of follicular T helper (Tfh) cells to support germinal center (GC) formation. However, it is not clear what unique functions programmed by BCL6 can explain its absolute essentiality in T cells for GC formation. We found that ablation of one Bcl6 allele did not appreciably alter early T cell activation and follicular localization but inhibited GC formation and Tfh cell maintenance. BCL6 impinged on Tfh calcium signaling and also controlled Tfh entanglement with and CD40L delivery to B cells. Amounts of BCL6 protein and nominal frequencies of Tfh cells markedly changed within hours after strengths of T-B cell interactions were altered in vivo, while CD40L overexpression rectified both defective GC formation and Tfh cell maintenance because of the BCL6 haploinsufficiency. Our results reveal BCL6 functions in Tfh cells that are essential for GC formation and suggest that BCL6 helps maintain Tfh cell phenotypes in a T cell non-autonomous manner.
•Both copies of Bcl6 gene are required for efficient follicular T-B cell entanglement•BCL6 is required for calcium signaling in Tfh cells and CD40L delivery to B cells•Expression of Tfh markers responds to acute perturbation of T-B cell interactions•Defective functions of BCL6-insufficient T cells are rescued by CD40L overexpression
BCL6 is required for Tfh cell development. Liu et al. show that BCL6 controls calcium signaling of Tfh cells, follicular T-B cell entanglement, and efficient T cell-to-B cell CD40L delivery and promotes Tfh cell maintenance partly in a T cell non-autonomous manner.</abstract><pub>Elsevier Inc</pub><pmid>34464595</pmid><doi>10.1016/j.immuni.2021.08.003</doi><orcidid>https://orcid.org/0000-0002-9596-7307</orcidid><orcidid>https://orcid.org/0000-0001-5475-3989</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | BCL6 calcium signaling CD40L follicle germinal center intravital imaging lymph node stim1 T-B interactions Tfh cells |
title | BCL6 controls contact-dependent help delivery during follicular T-B cell interactions |
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