{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T06:02:41Z","timestamp":1775368961696,"version":"3.50.1"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The polysaccharides (PS) surrounding encapsulated bacteria are generally unable to activate T cells and hence do not induce B cell memory (BMEM). PS conjugate vaccines recruit CD4+ T cells via a carrier protein, such as tetanus toxoid (TT), resulting in the induction of PS-specific BMEM. However, the requirement for T cells in the subsequent activation of the BMEM at the time of bacterial encounter is poorly understood, despite having critical implications for protection. We demonstrate that the PS-specific BMEM induced in humans by a meningococcal serogroup C PS (Men C)\u2013TT conjugate vaccine conform to the isotype-switched (IgG+CD27+) rather than the IgM memory (IgM+CD27+) phenotype. Both Men C and TT-specific BMEM require CD4+ T cells to differentiate into plasma cells. However, noncognate bystander T cells provide such signals to PS-specific BMEM with comparable effect to the cognate T cells available to TT-specific BMEM. The interaction between the two populations is contact-dependent and is mediated in part through CD40. Meningococci drive the differentiation of the Men C\u2013specific BMEM through the activation of bystander T cells by bacterial proteins, although these signals are enhanced by T cell\u2013independent innate signals. An effect of the TT-specific T cells activated by the vaccine on unrelated BMEM in vivo is also demonstrated. These data highlight that any protection conferred by PS-specific BMEM at the time of bacterial encounter will depend on the effectiveness with which bacterial proteins are able to activate bystander T cells. Priming for T cell memory against bacterial proteins through their inclusion in vaccine preparations must continue to be pursued.<\/jats:p>","DOI":"10.4049\/jimmunol.1203254","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T05:42:58Z","timestamp":1384407778000},"page":"6071-6083","source":"Crossref","is-referenced-by-count":16,"title":["Polysaccharide-Specific Memory B Cells Generated by Conjugate Vaccines in Humans Conform to the CD27+IgG+ Isotype\u2013Switched Memory B Cell Phenotype and Require Contact-Dependent Signals from Bystander T Cells Activated by Bacterial Proteins To Differentiate into Plasma Cells"],"prefix":"10.1093","volume":"191","author":[{"given":"Edward T","family":"Clarke","sequence":"first","affiliation":[{"name":"School of Cellular and Molecular Medicine, University of Bristol , Bristol BS8 1TD,","place":["United Kingdom"]},{"name":"Medical Research Council Unit\u2013The Gambia , Banjul, The Gambia, West Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil A","family":"Williams","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, University of Bristol , Bristol BS8 1TD,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Findlow","sequence":"additional","affiliation":[{"name":"Vaccine Evaluation Unit, Health Protection Agency, Public Health Laboratory, Manchester Royal Infirmary , Manchester M13 9WZ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ray","family":"Borrow","sequence":"additional","affiliation":[{"name":"Vaccine Evaluation Unit, Health Protection Agency, Public Health Laboratory, Manchester Royal Infirmary , Manchester M13 9WZ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert S","family":"Heyderman","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, University of Bristol , Bristol BS8 1TD,","place":["United Kingdom"]},{"name":"Malawi\u2013Liverpool\u2013Wellcome Trust Clinical Research Programme , Blantyre 3,","place":["Malawi"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Finn","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, University of Bristol , Bristol BS8 1TD,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,12,15]]},"reference":[{"key":"2025032406054713100_r1","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1093\/intimm\/10.11.1703","article-title":"Survival of long-lived plasma cells is independent of antigen","volume":"10","author":"Manz","year":"1998","journal-title":"Int. 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