{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:19:54Z","timestamp":1791206394451,"version":"4.1.0"},"reference-count":49,"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>CD4 T cell memory generation is shaped by a number of factors, including the strength and duration of TCR signaling, as well as the priming environment, all of which can be modified by B cells. Studies using B cell\u2013deficient mice indicate B cells play a critical role in generating effector and memory CD4 T cells; however, when and how B cells are acting to promote these responses has not yet been ascertained. In this study, we use anti-CD20 Ab depletion of B cells at different times following Listeria monocytogenes infection to show that B cells are necessary for the induction of optimal CD4 T cell memory, but not for the transition and maintenance of this population. Importantly, the prerequisite of B cells early postinfection is partially dependent on their expression of MHC class II. B cells are not only required during the priming phase, but also necessary for the initiation of robust secondary responses by memory CD4 T cells. Interestingly, the requirement during the recall response is independent of B cell Ag presentation. Overall, these studies demonstrate the temporally and functionally distinct roles for B cells in regulating CD4 T cell responses.<\/jats:p>","DOI":"10.4049\/jimmunol.1302033","type":"journal-article","created":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T04:38:25Z","timestamp":1384231105000},"page":"6052-6059","source":"Crossref","is-referenced-by-count":15,"title":["Temporal Requirements for B Cells in the Establishment of CD4 T Cell Memory"],"prefix":"10.1093","volume":"191","author":[{"given":"Sarah B","family":"Mollo","sequence":"first","affiliation":[{"name":"Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan J","family":"Zajac","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie E","family":"Harrington","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,12,15]]},"reference":[{"key":"2025032406075253600_r1","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1182\/blood-2008-05-078154","article-title":"CD4 T cells: fates, functions, and faults","volume":"112","author":"Zhu","year":"2008","journal-title":"Blood"},{"key":"2025032406075253600_r2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1126\/science.272.5258.54","article-title":"Immunological memory and protective immunity: understanding their relation","volume":"272","author":"Ahmed","year":"1996","journal-title":"Science"},{"key":"2025032406075253600_r3","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":"2025032406075253600_r4","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.4049\/jimmunol.164.5.2338","article-title":"Qualitative changes accompany memory T cell generation: faster, more effective responses at lower doses of antigen","volume":"164","author":"Rogers","year":"2000","journal-title":"J. Immunol."},{"key":"2025032406075253600_r5","doi-asserted-by":"crossref","first-page":"E2551","DOI":"10.1073\/pnas.1205894109","article-title":"Memory CD4+ T-cell-mediated protection depends on secondary effectors that are distinct from and superior to primary effectors","volume":"109","author":"Strutt","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032406075253600_r6","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.immuni.2009.10.011","article-title":"CD44 regulates survival and memory development in Th1 cells","volume":"32","author":"Baaten","year":"2010","journal-title":"Immunity"},{"key":"2025032406075253600_r7","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.0105-2896.2006.00401.x","article-title":"Homeostasis of memory T cells","volume":"211","author":"Surh","year":"2006","journal-title":"Immunol. Rev."},{"key":"2025032406075253600_r8","doi-asserted-by":"crossref","first-page":"61","DOI":"10.4049\/jimmunol.171.1.61","article-title":"Homeostasis of naive and memory CD4+ T cells: IL-2 and IL-7 differentially regulate the balance between proliferation and Fas-mediated apoptosis","volume":"171","author":"Jaleco","year":"2003","journal-title":"J. Immunol."},{"key":"2025032406075253600_r9","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.immuni.2012.09.020","article-title":"Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets","volume":"38","author":"Sathaliyawala","year":"2013","journal-title":"Immunity"},{"key":"2025032406075253600_r10","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.4049\/jimmunol.1102243","article-title":"Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection","volume":"187","author":"Teijaro","year":"2011","journal-title":"J. Immunol."},{"key":"2025032406075253600_r11","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nri3442","article-title":"The integration of T cell migration, differentiation and function","volume":"13","author":"Masopust","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"2025032406075253600_r12","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.clim.2008.01.011","article-title":"Rituximab-induced B cell depletion in autoimmune diseases: potential effects on T cells","volume":"127","author":"Liossis","year":"2008","journal-title":"Clin. Immunol."},{"key":"2025032406075253600_r13","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1365-2249.2009.03978.x","article-title":"Translational Mini-Review Series on B Cell-Directed Therapies: The pathogenic role of B cells in autoantibody-associated autoimmune diseases\u2014lessons from B cell-depletion therapy","volume":"157","author":"Leandro","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"2025032406075253600_r14","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2174\/187152612800564437","article-title":"Unraveling effector functions of B cells during infection: the hidden world beyond antibody production","volume":"12","author":"Le\u00f3n","year":"2012","journal-title":"Infect. Disord. Drug Targets"},{"key":"2025032406075253600_r15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jaci.2007.11.030","article-title":"B cell-directed therapies for autoimmune disease and correlates of disease response and relapse","volume":"121","author":"Levesque","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032406075253600_r16","doi-asserted-by":"crossref","first-page":"20878","DOI":"10.1073\/pnas.0709205105","article-title":"Therapeutic B cell depletion impairs adaptive and autoreactive CD4+ T cell activation in mice","volume":"104","author":"Bouaziz","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032406075253600_r17","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1084\/jem.20111675","article-title":"B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6-producing B cells","volume":"209","author":"Barr","year":"2012","journal-title":"J. Exp. Med."},{"key":"2025032406075253600_r18","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.immuni.2009.01.006","article-title":"Cytokine-producing effector B cells regulate type 2 immunity to H. polygyrus","volume":"30","author":"Wojciechowski","year":"2009","journal-title":"Immunity"},{"key":"2025032406075253600_r19","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.4049\/jimmunol.1001431","article-title":"TLR and B cell receptor signals to B cells differentially program primary and memory Th1 responses to Salmonella enterica","volume":"185","author":"Barr","year":"2010","journal-title":"J. Immunol."},{"key":"2025032406075253600_r20","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.4049\/jimmunol.176.6.3498","article-title":"Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells","volume":"176","author":"Crawford","year":"2006","journal-title":"J. Immunol."},{"key":"2025032406075253600_r21","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/ni.2309","article-title":"Regulation of T(H)2 development by CXCR5+ dendritic cells and lymphotoxin-expressing B cells","volume":"13","author":"Le\u00f3n","year":"2012","journal-title":"Nat. Immunol."},{"key":"2025032406075253600_r22","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1084\/jem.194.11.1649","article-title":"Splenic T zone development is B cell dependent","volume":"194","author":"Ngo","year":"2001","journal-title":"J. Exp. Med."},{"key":"2025032406075253600_r23","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1084\/jem.187.7.1009","article-title":"B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion","volume":"187","author":"Fu","year":"1998","journal-title":"J. Exp. Med."},{"key":"2025032406075253600_r24","doi-asserted-by":"crossref","first-page":"5926","DOI":"10.4049\/jimmunol.174.10.5926","article-title":"Cutting edge: emergence of CD127high functionally competent memory T cells is compromised by high viral loads and inadequate T cell help","volume":"174","author":"Fuller","year":"2005","journal-title":"J. Immunol."},{"key":"2025032406075253600_r25","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.4049\/jimmunol.171.3.1423","article-title":"Clearance of Pneumocystis carinii in mice is dependent on B cells but not on P carinii-specific antibody","volume":"171","author":"Lund","year":"2003","journal-title":"J. Immunol."},{"key":"2025032406075253600_r26","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1128\/IAI.68.1.46-53.2000","article-title":"Igh-6(-\/-) (B-cell-deficient) mice fail to mount solid acquired resistance to oral challenge with virulent Salmonella enterica serovar typhimurium and show impaired Th1 T-cell responses to Salmonella antigens","volume":"68","author":"Mastroeni","year":"2000","journal-title":"Infect. Immun."},{"key":"2025032406075253600_r27","doi-asserted-by":"crossref","first-page":"5558","DOI":"10.4049\/jimmunol.165.10.5558","article-title":"A critical role for B cells in the development of memory CD4 cells","volume":"165","author":"Linton","year":"2000","journal-title":"J. Immunol."},{"key":"2025032406075253600_r28","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.4049\/jimmunol.0802501","article-title":"Requirement of B cells for generating CD4+ T cell memory","volume":"182","author":"Whitmire","year":"2009","journal-title":"J. Immunol."},{"key":"2025032406075253600_r29","doi-asserted-by":"crossref","first-page":"3763","DOI":"10.1002\/(SICI)1521-4141(199811)28:11<3763::AID-IMMU3763>3.0.CO;2-D","article-title":"CD4+ T cell responses in mice lacking MHC class II molecules specifically on B cells","volume":"28","author":"Williams","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"2025032406075253600_r30","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1084\/jem.182.4.915","article-title":"Successful T cell priming in B cell-deficient mice","volume":"182","author":"Epstein","year":"1995","journal-title":"J. Exp. Med."},{"key":"2025032406075253600_r31","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.4049\/jimmunol.161.3.1439","article-title":"Gene knockout B cell-deficient mice demonstrate that B cells play an important role in the initiation of T cell responses to Chlamydia trachomatis (mouse pneumonitis) lung infection","volume":"161","author":"Yang","year":"1998","journal-title":"J. Immunol."},{"key":"2025032406075253600_r32","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/eji.1830111203","article-title":"Defective induction of antigen-reactive proliferating T cells in B cell-deprived mice","volume":"11","author":"Ron","year":"1981","journal-title":"Eur. J. Immunol."},{"key":"2025032406075253600_r33","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.4049\/jimmunol.138.9.2848","article-title":"T cell priming in vivo: a major role for B cells in presenting antigen to T cells in lymph nodes","volume":"138","author":"Ron","year":"1987","journal-title":"J. Immunol."},{"key":"2025032406075253600_r34","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.4049\/jimmunol.157.7.2947","article-title":"Quantitative analysis of the influenza virus-specific CD4+ T cell memory in the absence of B cells and Ig","volume":"157","author":"Topham","year":"1996","journal-title":"J. Immunol."},{"key":"2025032406075253600_r35","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1093\/intimm\/13.12.1583","article-title":"Role of B cells as antigen-presenting cells in vivo revisited: antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations","volume":"13","author":"Rivera","year":"2001","journal-title":"Int. Immunol."},{"key":"2025032406075253600_r36","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.coi.2010.10.007","article-title":"Regulation of T follicular helper cell formation and function by antigen presenting cells","volume":"23","author":"Deenick","year":"2011","journal-title":"Curr. Opin. Immunol."},{"key":"2025032406075253600_r37","doi-asserted-by":"crossref","first-page":"980","DOI":"10.4049\/jimmunol.135.2.980","article-title":"Antigen-specific B cells efficiently present low doses of antigen for induction of T cell proliferation","volume":"135","author":"Malynn","year":"1985","journal-title":"J. Immunol."},{"key":"2025032406075253600_r38","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.4049\/jimmunol.168.4.1723","article-title":"Repeated antigen exposure is necessary for the differentiation, but not the initial proliferation, of naive CD4(+) T cells","volume":"168","author":"Baj\u00e9noff","year":"2002","journal-title":"J. Immunol."},{"key":"2025032406075253600_r39","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1084\/jem.20042521","article-title":"Antigen persistence is required throughout the expansion phase of a CD4(+) T cell response","volume":"201","author":"Obst","year":"2005","journal-title":"J. Exp. Med."},{"key":"2025032406075253600_r40","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.immuni.2008.02.014","article-title":"Rapid culling of the CD4+ T cell repertoire in the transition from effector to memory","volume":"28","author":"Williams","year":"2008","journal-title":"Immunity"},{"key":"2025032406075253600_r41","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1365-2567.2010.03338.x","article-title":"Nature and nurture: T-cell receptor-dependent and T-cell receptor-independent differentiation cues in the selection of the memory T-cell pool","volume":"131","author":"Kim","year":"2010","journal-title":"Immunology"},{"key":"2025032406075253600_r42","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1365-2567.2010.03260.x","article-title":"Memory CD4 T cells: generation, reactivation and re-assignment","volume":"130","author":"MacLeod","year":"2010","journal-title":"Immunology"},{"key":"2025032406075253600_r43","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1084\/jem.20082039","article-title":"Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus","volume":"205","author":"Iijima","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025032406075253600_r44","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.cell.2012.08.015","article-title":"Chemokine guidance of central memory T cells is critical for antiviral recall responses in lymph nodes","volume":"150","author":"Sung","year":"2012","journal-title":"Cell"},{"key":"2025032406075253600_r45","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.immuni.2012.01.013","article-title":"B cell maintenance of subcapsular sinus macrophages protects against a fatal viral infection independent of adaptive immunity","volume":"36","author":"Moseman","year":"2012","journal-title":"Immunity"},{"key":"2025032406075253600_r46","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.trim.2013.04.008","article-title":"The effects of in vivo B-cell depleting therapy on ex-vivo cytokine production","volume":"28","author":"Smeekens","year":"2013","journal-title":"Transpl. Immunol."},{"key":"2025032406075253600_r47","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1002\/art.22505","article-title":"Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis","volume":"56","author":"Gunnarsson","year":"2007","journal-title":"Arthritis Rheum."},{"key":"2025032406075253600_r48","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/art.20858","article-title":"Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial","volume":"52","author":"Sfikakis","year":"2005","journal-title":"Arthritis Rheum."},{"key":"2025032406075253600_r49","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1136\/ard.2006.057885","article-title":"Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system","volume":"66","author":"Tokunaga","year":"2007","journal-title":"Ann. Rheum. Dis."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/12\/6052\/61537634\/1302033.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/12\/6052\/61537634\/1302033.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T19:11:26Z","timestamp":1742929886000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/191\/12\/6052\/7966674"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12]]},"references-count":49,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2013,12,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1302033","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,12]]},"published":{"date-parts":[[2013,12]]}}}