Follicular Helper T Cell Differentiation Requires Continuous Antigen Presentation that Is Independent of Unique B Cell Signaling
Effective humoral immunity depends on the support of B cell responses by T follicular helper (Tfh) cells. Although it has been proposed that Tfh cell differentiation requires T-B interactions, the relative contribution of specific populations of Ag-presenting cells remains unknown. We employed three...
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| Veröffentlicht in: | Immunity (Cambridge, Mass.) Mass.), 2010-08, Vol.33 (2), p.241-253 |
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| creator | Deenick, Elissa K. Chan, Anna Ma, Cindy S. Gatto, Dominique Schwartzberg, Pamela L. Brink, Robert Tangye, Stuart G. |
| description | Effective humoral immunity depends on the support of B cell responses by T follicular helper (Tfh) cells. Although it has been proposed that Tfh cell differentiation requires T-B interactions, the relative contribution of specific populations of Ag-presenting cells remains unknown. We employed three independent strategies that compromised interactions between CD4
+ T cells and activated B cells in vivo. Whereas the expansion of CD4
+ T cells was relatively unaffected, Tfh cell differentiation was completely blocked in all scenarios. Surprisingly, augmenting antigen presentation by non-B cells rescued Tfh cell differentiation, as determined by surface phenotype, gene expression, and germinal center localization. We conclude that although Ag presentation by responding B cells is typically required for the generation of Tfh cells, this does not result from the provision of a unique B cell-derived signal, but rather because responding B cells rapidly become the primary source of antigen.
[Display omitted]
► SAP deficiency impairs Tfh cell development ► Lack of Ag presentation by activated B cells impairs Tfh cell development ► Ag presentation by DCs is short-lived ► Prolonging Ag presentation by DCs abolishes the need for B cells in Tfh cell development |
| doi_str_mv | 10.1016/j.immuni.2010.07.015 |
| format | Article |
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+ T cells and activated B cells in vivo. Whereas the expansion of CD4
+ T cells was relatively unaffected, Tfh cell differentiation was completely blocked in all scenarios. Surprisingly, augmenting antigen presentation by non-B cells rescued Tfh cell differentiation, as determined by surface phenotype, gene expression, and germinal center localization. We conclude that although Ag presentation by responding B cells is typically required for the generation of Tfh cells, this does not result from the provision of a unique B cell-derived signal, but rather because responding B cells rapidly become the primary source of antigen.
[Display omitted]
► SAP deficiency impairs Tfh cell development ► Lack of Ag presentation by activated B cells impairs Tfh cell development ► Ag presentation by DCs is short-lived ► Prolonging Ag presentation by DCs abolishes the need for B cells in Tfh cell development</description><identifier>ISSN: 1074-7613</identifier><identifier>EISSN: 1097-4180</identifier><identifier>DOI: 10.1016/j.immuni.2010.07.015</identifier><identifier>PMID: 20691615</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Antigen Presentation ; B-Lymphocytes - immunology ; B-Lymphocytes - metabolism ; CD40 Antigens - immunology ; Cell Differentiation ; CELLIMMUNO ; Cells, Cultured ; Defects ; Gene Expression Regulation ; Germinal Center - cytology ; Germinal Center - immunology ; Immune system ; Intracellular Signaling Peptides and Proteins - deficiency ; Intracellular Signaling Peptides and Proteins - immunology ; Ligands ; Lymphocyte Activation ; Mice ; Mice, Knockout ; MOLIMMUNO ; Mutation ; Proto-Oncogene Proteins c-bcl-6 - immunology ; Proto-Oncogene Proteins c-bcl-6 - metabolism ; Rodents ; Signal Transduction ; Signaling Lymphocytic Activation Molecule Associated Protein ; T cell receptors ; T-Lymphocytes, Helper-Inducer - cytology ; T-Lymphocytes, Helper-Inducer - immunology</subject><ispartof>Immunity (Cambridge, Mass.), 2010-08, Vol.33 (2), p.241-253</ispartof><rights>2010 Elsevier Inc.</rights><rights>Copyright 2010 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Aug 27, 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-5982b1d12a36cbc427747f2b805e01b974c9d402098f18e15ac06afc925fcf963</citedby><cites>FETCH-LOGICAL-c522t-5982b1d12a36cbc427747f2b805e01b974c9d402098f18e15ac06afc925fcf963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.immuni.2010.07.015$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20691615$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Deenick, Elissa K.</creatorcontrib><creatorcontrib>Chan, Anna</creatorcontrib><creatorcontrib>Ma, Cindy S.</creatorcontrib><creatorcontrib>Gatto, Dominique</creatorcontrib><creatorcontrib>Schwartzberg, Pamela L.</creatorcontrib><creatorcontrib>Brink, Robert</creatorcontrib><creatorcontrib>Tangye, Stuart G.</creatorcontrib><title>Follicular Helper T Cell Differentiation Requires Continuous Antigen Presentation that Is Independent of Unique B Cell Signaling</title><title>Immunity (Cambridge, Mass.)</title><addtitle>Immunity</addtitle><description>Effective humoral immunity depends on the support of B cell responses by T follicular helper (Tfh) cells. Although it has been proposed that Tfh cell differentiation requires T-B interactions, the relative contribution of specific populations of Ag-presenting cells remains unknown. We employed three independent strategies that compromised interactions between CD4
+ T cells and activated B cells in vivo. Whereas the expansion of CD4
+ T cells was relatively unaffected, Tfh cell differentiation was completely blocked in all scenarios. Surprisingly, augmenting antigen presentation by non-B cells rescued Tfh cell differentiation, as determined by surface phenotype, gene expression, and germinal center localization. We conclude that although Ag presentation by responding B cells is typically required for the generation of Tfh cells, this does not result from the provision of a unique B cell-derived signal, but rather because responding B cells rapidly become the primary source of antigen.
[Display omitted]
► SAP deficiency impairs Tfh cell development ► Lack of Ag presentation by activated B cells impairs Tfh cell development ► Ag presentation by DCs is short-lived ► Prolonging Ag presentation by DCs abolishes the need for B cells in Tfh cell development</description><subject>Animals</subject><subject>Antigen Presentation</subject><subject>B-Lymphocytes - immunology</subject><subject>B-Lymphocytes - metabolism</subject><subject>CD40 Antigens - immunology</subject><subject>Cell Differentiation</subject><subject>CELLIMMUNO</subject><subject>Cells, Cultured</subject><subject>Defects</subject><subject>Gene Expression Regulation</subject><subject>Germinal Center - cytology</subject><subject>Germinal Center - immunology</subject><subject>Immune system</subject><subject>Intracellular Signaling Peptides and Proteins - deficiency</subject><subject>Intracellular Signaling Peptides and Proteins - immunology</subject><subject>Ligands</subject><subject>Lymphocyte Activation</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>MOLIMMUNO</subject><subject>Mutation</subject><subject>Proto-Oncogene Proteins c-bcl-6 - immunology</subject><subject>Proto-Oncogene Proteins c-bcl-6 - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Signaling Lymphocytic Activation Molecule Associated Protein</subject><subject>T cell receptors</subject><subject>T-Lymphocytes, Helper-Inducer - cytology</subject><subject>T-Lymphocytes, Helper-Inducer - immunology</subject><issn>1074-7613</issn><issn>1097-4180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk1v1DAQjRCIlsI_QMgSB067jB07ji9I7ULpSpVA0J4tx5lsvUrsrZ1U4sZPx1FK-TjAxR6N3zzPvHlF8ZLCmgKt3u7Xbhgm79YMcgrkGqh4VBxTUHLFaQ2P51jylaxoeVQ8S2kPQLlQ8LQ4YlApWlFxXHw_D33v7NSbSC6wP2AkV2SDfU_eu67DiH50ZnTBky94O7mIiWxCzvkpTImc5miHnnzO-YxcgOONGck2ka1v8YD58CMJHbn27nZCcrawf3U7b3rnd8-LJ53pE764v0-K6_MPV5uL1eWnj9vN6eXKCsbGlVA1a2hLmSkr21jOpOSyY00NAoE2SnKrWg4MVN3RGqkwFirTWcVEZztVlSfFu4X3MDUDtjZ3FU2vD9ENJn7TwTj954t3N3oX7nTJyxKqmeDNPUEMeZA06sElm2cxHrMWWmXNRV1L8V-k5ApoydmMfP0Xch-mmIVJmgrgrKqVYhnFF5SNIaWI3UPXFPTsBb3Xixf07AUNUmcv5LJXv0_8UPRz-b8kwaz7ncOok3XoLbZ5z3bUbXD__uEHfUHIqA</recordid><startdate>20100827</startdate><enddate>20100827</enddate><creator>Deenick, Elissa K.</creator><creator>Chan, Anna</creator><creator>Ma, Cindy S.</creator><creator>Gatto, Dominique</creator><creator>Schwartzberg, Pamela L.</creator><creator>Brink, Robert</creator><creator>Tangye, Stuart G.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100827</creationdate><title>Follicular Helper T Cell Differentiation Requires Continuous Antigen Presentation that Is Independent of Unique B Cell Signaling</title><author>Deenick, Elissa K. ; 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Although it has been proposed that Tfh cell differentiation requires T-B interactions, the relative contribution of specific populations of Ag-presenting cells remains unknown. We employed three independent strategies that compromised interactions between CD4
+ T cells and activated B cells in vivo. Whereas the expansion of CD4
+ T cells was relatively unaffected, Tfh cell differentiation was completely blocked in all scenarios. Surprisingly, augmenting antigen presentation by non-B cells rescued Tfh cell differentiation, as determined by surface phenotype, gene expression, and germinal center localization. We conclude that although Ag presentation by responding B cells is typically required for the generation of Tfh cells, this does not result from the provision of a unique B cell-derived signal, but rather because responding B cells rapidly become the primary source of antigen.
[Display omitted]
► SAP deficiency impairs Tfh cell development ► Lack of Ag presentation by activated B cells impairs Tfh cell development ► Ag presentation by DCs is short-lived ► Prolonging Ag presentation by DCs abolishes the need for B cells in Tfh cell development</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20691615</pmid><doi>10.1016/j.immuni.2010.07.015</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigen Presentation B-Lymphocytes - immunology B-Lymphocytes - metabolism CD40 Antigens - immunology Cell Differentiation CELLIMMUNO Cells, Cultured Defects Gene Expression Regulation Germinal Center - cytology Germinal Center - immunology Immune system Intracellular Signaling Peptides and Proteins - deficiency Intracellular Signaling Peptides and Proteins - immunology Ligands Lymphocyte Activation Mice Mice, Knockout MOLIMMUNO Mutation Proto-Oncogene Proteins c-bcl-6 - immunology Proto-Oncogene Proteins c-bcl-6 - metabolism Rodents Signal Transduction Signaling Lymphocytic Activation Molecule Associated Protein T cell receptors T-Lymphocytes, Helper-Inducer - cytology T-Lymphocytes, Helper-Inducer - immunology |
| title | Follicular Helper T Cell Differentiation Requires Continuous Antigen Presentation that Is Independent of Unique B Cell Signaling |
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