{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:01:56Z","timestamp":1791190916327,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T00:00:00Z","timestamp":1298937600000},"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":[[2011,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CD4 T cell help for B cells is critical for effective Ab responses. Although many of the molecules involved in helper functions of naive CD4 T cells have been characterized, much less is known about the helper capabilities of memory CD4 T cells, an important consideration for the design of vaccines that aim to prime protective memory CD4 T cells. In this study, we demonstrate that memory CD4 T cells enable B cells to expand more rapidly and class switch earlier than do primary responding CD4 T cells. This accelerated response does not require large numbers of memory cells, and similar numbers of primary responding cells provide less effective help than do memory cells. However, only memory CD4 T cells that express the B cell follicle homing molecule, CXCR5, are able to accelerate the response, suggesting that the rapidity of the Ab response depends on the ability of CD4 memory T cells to migrate quickly toward B cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1002955","type":"journal-article","created":{"date-parts":[[2011,1,27]],"date-time":"2011-01-27T01:59:55Z","timestamp":1296093595000},"page":"2889-2896","source":"Crossref","is-referenced-by-count":131,"title":["Memory CD4 T Cells That Express CXCR5 Provide Accelerated Help to B Cells"],"prefix":"10.1093","volume":"186","author":[{"given":"Megan K L","family":"MacLeod","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Integrated Department of Immunology, National Jewish Health , Denver, CO 80206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandria","family":"David","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Integrated Department of Immunology, National Jewish Health , Denver, CO 80206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S","family":"McKee","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Integrated Department of Immunology, National Jewish Health , Denver, CO 80206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Crawford","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Integrated Department of Immunology, National Jewish Health , Denver, CO 80206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W","family":"Kappler","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Integrated Department of Immunology, National Jewish Health , Denver, CO 80206"},{"name":"Program in Biomolecular Structure, University of Colorado Denver, School of Medicine , Aurora, CO 80045"},{"name":"Department of Medicine, University of Colorado Denver, School of Medicine , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa","family":"Marrack","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Integrated Department of Immunology, National Jewish Health , Denver, CO 80206"},{"name":"Department of Medicine, University of Colorado Denver, School of Medicine , Aurora, CO 80045"},{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado Denver, School of Medicine , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,3,1]]},"reference":[{"key":"2025032411093818700_r1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.smim.2009.02.006","article-title":"CD4 memory T cells: what are they and what can they do?","volume":"21","author":"MacLeod","year":"2009","journal-title":"Semin. Immunol."},{"key":"2025032411093818700_r2","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1126\/science.1124228","article-title":"Naive and memory CD4+ T cell survival controlled by clonal abundance","volume":"312","author":"Hataye","year":"2006","journal-title":"Science"},{"key":"2025032411093818700_r3","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/90950","article-title":"Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory","volume":"7","author":"Homann","year":"2001","journal-title":"Nat. Med."},{"key":"2025032411093818700_r4","doi-asserted-by":"crossref","first-page":"14521","DOI":"10.1073\/pnas.0807449105","article-title":"CD4 memory T cells divide poorly in response to antigen because of their cytokine profile","volume":"105","author":"MacLeod","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032411093818700_r5","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1046\/j.1365-2567.2002.01447.x","article-title":"Qualitative differences between naive and memory T cells","volume":"106","author":"Berard","year":"2002","journal-title":"Immunology"},{"key":"2025032411093818700_r6","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.vaccine.2009.10.103","article-title":"Universal influenza DNA vaccine encoding conserved CD4+ T cell epitopes protects against lethal viral challenge in HLA-DR transgenic mice","volume":"28","author":"Alexander","year":"2010","journal-title":"Vaccine"},{"key":"2025032411093818700_r7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2567.2010.03259.x","article-title":"The potential of CD4 T-cell memory","volume":"130","author":"McKinstry","year":"2010","journal-title":"Immunology"},{"key":"2025032411093818700_r8","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1600-065X.1997.tb00958.x","article-title":"The changing preference of T and B cells for partners as T-dependent antibody responses develop","volume":"156","author":"MacLennan","year":"1997","journal-title":"Immunol. Rev."},{"key":"2025032411093818700_r9","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.immuni.2009.03.003","article-title":"Follicular helper T cells: lineage and location","volume":"30","author":"Fazilleau","year":"2009","journal-title":"Immunity"},{"key":"2025032411093818700_r10","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1086\/589862","article-title":"Vaccines: correlates of vaccine-induced immunity","volume":"47","author":"Plotkin","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"2025032411093818700_r11","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1084\/jem.132.2.261","article-title":"Carrier function in anti-hapten immune responses, I: Enhancement of primary and secondary anti-hapten antibody responses by carrier preimmunization","volume":"132","author":"Katz","year":"1970","journal-title":"J. Exp. Med."},{"key":"2025032411093818700_r12","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/eji.1830010412","article-title":"The effect of carrier-primed cells on an adoptive anti-hapten response","volume":"1","author":"Kontiainen","year":"1971","journal-title":"Eur. J. Immunol."},{"key":"2025032411093818700_r13","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1002\/eji.1830250919","article-title":"Stimulation of a memory B cell response does not require primed helper T cells","volume":"25","author":"Leclerc","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"2025032411093818700_r14","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.4049\/jimmunol.107.4.1137","article-title":"Regulation of homocytotropic antibody formation in the rat, V: Cell cooperation in the anti-hapten homocytotropic antibody response","volume":"107","author":"Tada","year":"1971","journal-title":"J. Immunol."},{"key":"2025032411093818700_r15","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1073\/pnas.83.8.2604","article-title":"Primary antibody responses to a well-defined and unique hapten are not enhanced by preimmunization with carrier: analysis in a viral model","volume":"83","author":"Gupta","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032411093818700_r16","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1084\/jem.190.8.1123","article-title":"In vivo-activated CD4 T cells upregulate CXC chemokine receptor 5 and reprogram their response to lymphoid chemokines","volume":"190","author":"Ansel","year":"1999","journal-title":"J. Exp. Med."},{"key":"2025032411093818700_r17","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1126\/science.1176676","article-title":"Bcl6 mediates the development of T follicular helper cells","volume":"325","author":"Nurieva","year":"2009","journal-title":"Science"},{"key":"2025032411093818700_r18","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1126\/science.1175870","article-title":"Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation","volume":"325","author":"Johnston","year":"2009","journal-title":"Science"},{"key":"2025032411093818700_r19","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.immuni.2009.07.002","article-title":"The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment","volume":"31","author":"Yu","year":"2009","journal-title":"Immunity"},{"key":"2025032411093818700_r20","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1084\/jem.192.11.1553","article-title":"CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function","volume":"192","author":"Schaerli","year":"2000","journal-title":"J. Exp. Med."},{"key":"2025032411093818700_r21","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/ni1472","article-title":"Lymphoid reservoirs of antigen-specific memory T helper cells","volume":"8","author":"Fazilleau","year":"2007","journal-title":"Nat. Immunol."},{"key":"2025032411093818700_r22","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.cell.2005.05.013","article-title":"How the T cell repertoire becomes peptide and MHC specific","volume":"122","author":"Huseby","year":"2005","journal-title":"Cell"},{"key":"2025032411093818700_r23","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S1074-7613(00)80572-5","article-title":"Detection of antigen-specific T cells with multivalent soluble class II MHC covalent peptide complexes","volume":"8","author":"Crawford","year":"1998","journal-title":"Immunity"},{"key":"2025032411093818700_r24","doi-asserted-by":"crossref","first-page":"4403","DOI":"10.4049\/jimmunol.0900164","article-title":"Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity","volume":"183","author":"McKee","year":"2009","journal-title":"J. Immunol."},{"key":"2025032411093818700_r25","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1084\/jem.20001021","article-title":"Estimating the precursor frequency of naive antigen-specific CD8 T cells","volume":"195","author":"Blattman","year":"2002","journal-title":"J. Exp. Med."},{"key":"2025032411093818700_r26","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.4049\/jimmunol.176.5.3028","article-title":"Precursor frequency, nonlinear proliferation, and functional maturation of virus-specific CD4+ T cells","volume":"176","author":"Whitmire","year":"2006","journal-title":"J. Immunol."},{"key":"2025032411093818700_r27","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/ni.1877","article-title":"PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells","volume":"11","author":"Good-Jacobson","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025032411093818700_r28","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.immuni.2010.01.010","article-title":"Optimal germinal center responses require a multistage T cell:B cell adhesion process involving integrins, SLAM-associated protein, and CD84","volume":"32","author":"Cannons","year":"2010","journal-title":"Immunity"},{"key":"2025032411093818700_r29","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1084\/jem.20090313","article-title":"IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells","volume":"206","author":"King","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025032411093818700_r30","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1084\/jem.20090303","article-title":"T follicular helper cells differentiate from Th2 cells in response to helminth antigens","volume":"206","author":"Zaretsky","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025032411093818700_r31","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1084\/jem.20091738","article-title":"IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses","volume":"207","author":"Linterman","year":"2010","journal-title":"J. Exp. Med."},{"key":"2025032411093818700_r32","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1146\/annurev.immunol.18.1.275","article-title":"CD8+ T cell effector mechanisms in resistance to infection","volume":"18","author":"Harty","year":"2000","journal-title":"Annu. Rev. Immunol."},{"key":"2025032411093818700_r33","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/nm917","article-title":"Duration of antiviral immunity after smallpox vaccination","volume":"9","author":"Hammarlund","year":"2003","journal-title":"Nat. Med."},{"key":"2025032411093818700_r34","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nri1052","article-title":"Cytokine control of memory T-cell development and survival","volume":"3","author":"Schluns","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2025032411093818700_r35","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1002\/eji.200939531","article-title":"Memory B cells: effectors of long-lived immune responses","volume":"39","author":"Tangye","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"2025032411093818700_r36","doi-asserted-by":"crossref","first-page":"6655","DOI":"10.4049\/jimmunol.169.12.6655","article-title":"Cutting edge: virus-specific CD4+ memory T cells in nonlymphoid tissues express a highly activated phenotype","volume":"169","author":"Cauley","year":"2002","journal-title":"J. Immunol."},{"key":"2025032411093818700_r37","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1084\/jem.20050711","article-title":"CD4 memory T cells survive and proliferate but fail to differentiate in the absence of CD40","volume":"203","author":"MacLeod","year":"2006","journal-title":"J. Exp. Med."},{"key":"2025032411093818700_r38","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1086\/424571","article-title":"Decrease in measles virus-specific CD4 T cell memory in vaccinated subjects","volume":"190","author":"Naniche","year":"2004","journal-title":"J. Infect. Dis."},{"key":"2025032411093818700_r39","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1084\/jem.20030091","article-title":"Activation of virus-specific memory B cells in the absence of T cell help","volume":"199","author":"Hebeis","year":"2004","journal-title":"J. Exp. Med."},{"key":"2025032411093818700_r40","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/ni1105","article-title":"CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection","volume":"5","author":"Sun","year":"2004","journal-title":"Nat. Immunol."},{"key":"2025032411093818700_r41","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1741-7007-8-37","article-title":"Immune mechanisms of protection: can adjuvants rise to the challenge?","volume":"8","author":"McKee","year":"2010","journal-title":"BMC Biol."},{"key":"2025032411093818700_r42","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1111\/j.1365-2567.2006.02446.x","article-title":"Naive T-cell receptor transgenic T cells help memory B cells produce antibody","volume":"119","author":"Duffy","year":"2006","journal-title":"Immunology"},{"key":"2025032411093818700_r43","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.immuni.2009.03.015","article-title":"Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow","volume":"30","author":"Tokoyoda","year":"2009","journal-title":"Immunity"},{"key":"2025032411093818700_r44","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.coi.2006.02.005","article-title":"B cell migration and interactions in the early phase of antibody responses","volume":"18","author":"Okada","year":"2006","journal-title":"Curr. Opin. Immunol."},{"key":"2025032411093818700_r45","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/ni.1715","article-title":"Cytokine-secreting follicular T cells shape the antibody repertoire","volume":"10","author":"Reinhardt","year":"2009","journal-title":"Nat. Immunol."},{"key":"2025032411093818700_r46","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/ni.1866","article-title":"Sustained signaling by canonical helper T cell cytokines throughout the reactive lymph node","volume":"11","author":"Perona-Wright","year":"2010","journal-title":"Nat. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/186\/5\/2889\/62470583\/1002955.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/186\/5\/2889\/62470583\/1002955.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T10:37:37Z","timestamp":1743158257000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/186\/5\/2889\/7990003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,1]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,3,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1002955","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,3]]},"published":{"date-parts":[[2011,3,1]]}}}