{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T05:01:12Z","timestamp":1772082072276,"version":"3.50.1"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2018,1,2]],"date-time":"2018-01-02T00:00:00Z","timestamp":1514851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Leicester Haematology Research Fund"},{"name":"Elimination of Leukaemia Fund"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0190468","type":"journal-article","created":{"date-parts":[[2018,1,2]],"date-time":"2018-01-02T20:13:12Z","timestamp":1514923992000},"page":"e0190468","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Circulating Tfh1 (cTfh1) cell numbers and PD1 expression are elevated in low-grade B-cell non-Hodgkin\u2019s lymphoma and cTfh gene expression is perturbed in marginal zone lymphoma"],"prefix":"10.1371","volume":"13","author":[{"given":"Elliot T.","family":"Byford","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Carr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Ladikou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J.","family":"Ahearne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8914-0370","authenticated-orcid":true,"given":"Simon D.","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2018,1,2]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.pharmthera.2014.07.003","article-title":"Microenvironment dependency in Chronic Lymphocytic Leukemia: The basis for new targeted therapies","volume":"144","author":"E Hacken ten","year":"2014","journal-title":"Pharmacology and Therapeutics"},{"key":"ref2","first-page":"1","article-title":"The microenvironment in chronic lymphocytic leukemia (CLL) and other B cell malignancies: Insight into disease biology and new targeted therapies","author":"JA Burger","year":"2013","journal-title":"Semin Cancer Biol. Elsevier Ltd"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"5052","DOI":"10.1200\/JCO.2006.06.4642","article-title":"Number of CD4+ cells and location of forkhead box protein P3-positive cells in diagnostic follicular lymphoma tissue microarrays correlates with outcome","volume":"24","author":"AM Lee","year":"2006","journal-title":"J Clin Oncol"},{"key":"ref4","first-page":"2957","article-title":"High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma","volume":"108","author":"J Carreras","year":"2006","journal-title":"Blood. American Society of Hematology"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1200\/JCO.2008.18.0513","article-title":"High numbers of tumor-infiltrating programmed cell death 1-positive regulatory lymphocytesare associated with improved overall survival in follicular lymphoma","volume":"27","author":"J Carreras","year":"2009","journal-title":"J Clin Oncol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1038\/leu.2011.301","article-title":"Characterization of intratumoral follicular helper T cells in follicular lymphoma: role in the survival of malignant B cells","volume":"26","author":"P Am\u00e9-Thomas","year":"2012","journal-title":"Leukemia"},{"key":"ref7","first-page":"1","article-title":"Follicular lymphoma cell niche: identification of a preeminent IL-4-dependent TFH\u2013B cell axis","author":"C Pangault","year":"2010","journal-title":"Leukemia"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/bjh.12401","article-title":"Enhancement of CD154\/IL4 proliferation by the T follicular helper (Tfh) cytokine, IL21 and increased numbers of circulating cells resembling Tfh cells in chronic lymphocytic leukaemia","volume":"162","author":"MJ Ahearne","year":"2013","journal-title":"Br J Haematol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1182\/blood-2012-11-467670","article-title":"IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of CLL cells","volume":"122","author":"MF Pascutti","year":"2013","journal-title":"Blood"},{"key":"ref10","first-page":"566","article-title":"Chronic Lymphocytic Leukemia Cells Are Activated and Proliferate in Response to Specific T Helper Cells","volume":"4","author":"A Os","year":"2013","journal-title":"CellReports. The Authors"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1182\/blood-2015-11-624312","article-title":"Splenic marginal zone lymphoma: from genetics to management","volume":"127","author":"L Arcaini","year":"2016","journal-title":"Blood"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"5207","DOI":"10.1158\/1078-0432.CCR-14-0496","article-title":"Emerging Role of Infectious Etiologies in the Pathogenesis of Marginal Zone B-cell Lymphomas","volume":"20","author":"E Zucca","year":"2014","journal-title":"Clin Cancer Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1146\/annurev-immunol-041015-055605","article-title":"Follicular Helper T Cells","volume":"34","author":"CG Vinuesa","year":"2016","journal-title":"Annu Rev Immunol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nm.2425","article-title":"Foxp3+ follicular regulatory T cells control the germinal center response","volume":"17","author":"MA Linterman","year":"2011","journal-title":"Nat Med. Nature Publishing Group"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/nm.2426","article-title":"Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions","volume":"17","author":"Y Chung","year":"2011","journal-title":"Nat Med"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1182\/blood.V84.3.830.bloodjournal843830","article-title":"Expression of the G-protein\u2014coupled receptor BLR1 defines mature, recirculating B cells and a subset of T-helper memory cells","volume":"84","author":"R F\u00f6rster","year":"1994","journal-title":"Blood"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.immuni.2010.12.012","article-title":"Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion","volume":"34","author":"R Morita","year":"2011","journal-title":"Immunity"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.immuni.2013.09.007","article-title":"Circulating precursor CCR7(lo)PD-1(hi) CXCR5\u207a CD4\u207a T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure","volume":"39","author":"J He","year":"2013","journal-title":"Immunity"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"5191","DOI":"10.1172\/JCI76861","article-title":"Circulating T follicular regulatory and helper cells have memory-like properties","volume":"124","author":"PT Sage","year":"2014","journal-title":"J Clin Invest"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.it.2014.06.002","article-title":"Phenotype and functions of memory Tfh cells in human blood","volume":"35","author":"N Schmitt","year":"2014","journal-title":"Trends in Immunology. Elsevier Ltd"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1084\/jem.187.6.875","article-title":"Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes","volume":"187","author":"F Sallusto","year":"1998","journal-title":"J Exp Med"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/ni1467","article-title":"Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells","volume":"8","author":"EV Acosta-Rodriguez","year":"2007","journal-title":"Nat Immunol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3389\/fimmu.2014.00276","article-title":"Th17 cells in cancer: the ultimate identity crisis","volume":"5","author":"SR Bailey","year":"2014","journal-title":"Front Immunol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"120","DOI":"10.4049\/jimmunol.1302734","article-title":"IL-1\u03b2 promotes the differentiation of polyfunctional human CCR6+CXCR3+ Th1\/17 cells that are specific for pathogenic and commensal microbes","volume":"193","author":"T Duhen","year":"2014","journal-title":"J Immunol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"7541","DOI":"10.1007\/s13277-014-1999-5","article-title":"Alterations of circulating follicular helper T cells and interleukin 21 in diffuse large B-cell lymphoma","volume":"35","author":"Z Cha","year":"2014","journal-title":"Tumour Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"176ra32","DOI":"10.1126\/scitranslmed.3005191","article-title":"Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination","volume":"5","author":"SE Bentebibel","year":"2013","journal-title":"Science Translational Medicine"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nbt.2594","article-title":"viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia","volume":"31","author":"E-AD Amir","year":"2013","journal-title":"Nat Biotechnol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1182\/blood-2015-12-688895","article-title":"Circulating T follicular helper cells with increased function during chronic graft-versus-host disease","volume":"127","author":"E Forcade","year":"2016","journal-title":"Blood"},{"key":"ref29","article-title":"Defective TFH Cell Function and Increased TFR Cells Contribute to Defective Antibody Production in Aging","author":"PT Sage","year":"2015","journal-title":"CellReports"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1742-4933-11-12","article-title":"The effect of aging on the frequency, phenotype and cytokine production of human blood CD4 + CXCR5 + T follicular helper cells: comparison of aged and young subjects","volume":"11","author":"M Zhou","year":"2014","journal-title":"Immun Ageing. BioMed Central"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e75319","DOI":"10.1371\/journal.pone.0075319","article-title":"Circulating TFH subset distribution is strongly affected in lupus patients with an active disease","volume":"8","author":"C Le Coz","year":"2013","journal-title":"PLoS ONE"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.4049\/jimmunol.1302503","article-title":"Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults","volume":"193","author":"RS Herati","year":"2014","journal-title":"J Immunol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/icb.2013.77","article-title":"How T follicular helper cells and the germinal centre response change with age","volume":"92","author":"MA Linterman","year":"2014","journal-title":"Immunol Cell Biol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"4927","DOI":"10.4049\/jimmunol.177.7.4927","article-title":"ICOS deficiency is associated with a severe reduction of CXCR5+CD4 germinal center Th cells","volume":"177","author":"L Bossaller","year":"2006","journal-title":"The Journal of Immunology"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/s41467-017-00843-7","article-title":"Interconnected subsets of memory follicular helper T cells have different effector functions","volume":"8","author":"A Asrir","year":"2017","journal-title":"Nature Communications. Nature Publishing Group"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/ni.3054","article-title":"Pathophysiology of T follicular helper cells in humans and mice","volume":"16","author":"H Ueno","year":"2015","journal-title":"Nat Immunol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.bbrc.2012.04.133","article-title":"Role of the frequency of blood CD4+ CXCR5+ CCR6+ T cells in autoimmunity in patients with Sj\u00f6gren\u2019s syndrome","volume":"422","author":"X-Y Li","year":"2012","journal-title":"BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. Elsevier Inc"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"e57820","DOI":"10.1371\/journal.pone.0057820","article-title":"Systemic inflammation in progressive multiple sclerosis involves follicular T-helper, Th17- and activated B-cells and correlates with progression","volume":"8","author":"J Romme Christensen","year":"2013","journal-title":"PLoS ONE"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.yexcr.2016.11.017","article-title":"Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway","volume":"350","author":"Z Cha","year":"2017","journal-title":"Experimental Cell Research"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e89574","DOI":"10.1172\/jci.insight.89574","article-title":"Circulating CXCR5(+)CXCR3(+)PD-1(lo) Tfh-like cells in HIV-1 controllers with neutralizing antibody breadth","volume":"2","author":"E Martin-Gayo","year":"2017","journal-title":"JCI Insight"},{"key":"ref41","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":"RL Reinhardt","year":"2009","journal-title":"Nat Immunol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/ajcp\/95.1.55","article-title":"Interleukin-2 and interferon-gamma production in follicular lymphomas","volume":"95","author":"M Peuchmaur","year":"1991","journal-title":"Am J Clin Pathol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s002620000127","article-title":"Expression of genes coding for the tumor necrosis factor and lymphotoxin ligand-receptor system in non-Hodgkin\u2019s lymphomas","volume":"49","author":"K Warzocha","year":"2000","journal-title":"Cancer Immunol Immunother"},{"key":"ref44","first-page":"580","article-title":"Localization in situ of costimulatory molecules and cytokines in B-cell non-Hodgkin\u2019s lymphoma","volume":"94","author":"FA Vyth-Dreese","year":"1998","journal-title":"Immunology. Wiley-Blackwell"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1080\/00365520152584842","article-title":"CD4+ Th1-cells predominate in low-grade B-cell lymphoma of gastric mucosa-associated lymphoid tissue (MALT type)","volume":"36","author":"S Riedel","year":"2001","journal-title":"Scand J Gastroenterol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jaut.2015.07.002","article-title":"Type I and II interferon signatures in Sjogren\u201cs syndrome pathogenesis: Contributions in distinct clinical phenotypes and Sjogren\u201ds related lymphomagenesis","volume":"63","author":"A Nezos","year":"2015","journal-title":"Journal of Autoimmunity"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1084\/jem.20151724","article-title":"B cell IFN-\u03b3 receptor signaling promotes autoimmune germinal centers via cell-intrinsic induction of BCL-6","volume":"213","author":"SW Jackson","year":"2016","journal-title":"J Exp Med"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1126\/science.285.5425.260","article-title":"BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator","volume":"285","author":"PA Moore","year":"1999","journal-title":"Science"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1084\/jem.189.11.1747","article-title":"BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth","volume":"189","author":"P Schneider","year":"1999","journal-title":"J Exp Med"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1084\/jem.20100086","article-title":"Myeloid cells, BAFF, and IFN-\u03b3 establish an inflammatory loop that exacerbates autoimmunity in Lyn-deficient mice","volume":"207","author":"P Scapini","year":"2010","journal-title":"J Exp Med"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.humpath.2005.08.005","article-title":"BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders","volume":"36","author":"SJ Rodig","year":"2005","journal-title":"Hum Pathol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1182\/blood-2004-02-0762","article-title":"Expression of BLyS and its receptors in B-cell non-Hodgkin lymphoma: correlation with disease activity and patient outcome","volume":"104","author":"AJ Novak","year":"2004","journal-title":"Blood"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1158\/1055-9965.EPI-09-1237","article-title":"Plasma cytokines and future risk of non-Hodgkin lymphoma (NHL): a case-control study nested in the Italian European Prospective Investigation into Cancer and Nutrition","volume":"19","author":"F Saberi Hosnijeh","year":"2010","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.immuni.2008.04.016","article-title":"Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation","volume":"28","author":"M Shi","year":"2008","journal-title":"Immunity"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0190468","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,25]],"date-time":"2020-10-25T04:05:55Z","timestamp":1603598755000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0190468"}},"subtitle":[],"editor":[{"given":"Yolande","family":"Richard","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,1,2]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,1,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0190468","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,2]]}}}