{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:35:07Z","timestamp":1779244507241,"version":"3.51.4"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T00:00:00Z","timestamp":1619740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T00:00:00Z","timestamp":1619740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["100693"],"award-info":[{"award-number":["100693"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"published-print":{"date-parts":[[2021,8]]},"DOI":"10.1007\/s10875-021-01031-5","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T13:04:06Z","timestamp":1619787846000},"page":"1272-1290","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Genomic Spectrum and Phenotypic Heterogeneity of Human IL-21 Receptor Deficiency"],"prefix":"10.1007","volume":"41","author":[{"given":"Deniz","family":"Cagdas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Mayr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Safa","family":"Baris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Worley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B.","family":"Langley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayse","family":"Metin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elif Soyak","family":"Aytekin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raziye","family":"Atan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurhan","family":"Kasap","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sevgi K\u00f6stel","family":"Bal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmin","family":"Dmytrus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul Jimenez","family":"Heredia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulsun","family":"Karasu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selda Hancerli","family":"Torun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muge","family":"Toyran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elif","family":"Karakoc-Aydiner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Christ","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baris","family":"Kuskonmaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duygu","family":"U\u00e7kan-\u00c7etinkaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aysegul","family":"Uner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felicitas","family":"Oberndorfer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana-Iris","family":"Schiefer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulbu","family":"Uzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elissa K.","family":"Deenick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baerbel","family":"Keller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Warnatz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9n\u00e9dicte","family":"Neven","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Durandy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozden","family":"Sanal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy S.","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmet","family":"\u00d6zen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Polina","family":"Stepensky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilhan","family":"Tezcan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaan","family":"Boztug","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5360-5180","authenticated-orcid":false,"given":"Stuart G.","family":"Tangye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,30]]},"reference":[{"issue":"4","key":"1031_CR1","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1016\/j.jaci.2016.06.033","volume":"138","author":"M Akdis","year":"2016","unstructured":"Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor \u03b2, and TNF-\u03b1: receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2016;138(4):984\u20131010. https:\/\/doi.org\/10.1016\/j.jaci.2016.06.033.","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"1031_CR2","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.4049\/jimmunol.1700842","volume":"199","author":"SG Tangye","year":"2017","unstructured":"Tangye SG, Pelham SJ, Deenick EK, Ma CS. Cytokine-mediated regulation of human lymphocyte development and function: insights from primary immunodeficiencies. J Immunol. 2017;199(6):1949\u201358. https:\/\/doi.org\/10.4049\/jimmunol.1700842.","journal-title":"J Immunol"},{"issue":"1","key":"1031_CR3","doi-asserted-by":"publisher","first-page":"68","DOI":"10.4049\/jimmunol.173.1.68","volume":"173","author":"T Chtanova","year":"2004","unstructured":"Chtanova T, Tangye SG, Newton R, Frank N, Hodge MR, Rolph MS, et al. T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1\/Th2 effector cells that provide help for B cells. J Immunol. 2004;173(1):68\u201378. https:\/\/doi.org\/10.4049\/jimmunol.173.1.68.","journal-title":"J Immunol"},{"issue":"48","key":"1031_CR4","doi-asserted-by":"publisher","first-page":"34605","DOI":"10.1074\/jbc.M705100200","volume":"282","author":"L Wei","year":"2007","unstructured":"Wei L, Laurence A, Elias KM, O'Shea JJ. IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. J Biol Chem. 2007;282(48):34605\u201310. https:\/\/doi.org\/10.1074\/jbc.M705100200.","journal-title":"J Biol Chem"},{"issue":"1","key":"1031_CR5","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1093\/intimm\/dxp112","volume":"22","author":"R Spolski","year":"2010","unstructured":"Spolski R, Leonard WJ. IL-21 and T follicular helper cells. Int Immunol. 2010;22(1):7\u201312.","journal-title":"Int Immunol"},{"issue":"5","key":"1031_CR6","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.4049\/jimmunol.178.5.2827","volume":"178","author":"JM Coquet","year":"2007","unstructured":"Coquet JM, Kyparissoudis K, Pellicci DG, Besra G, Berzins SP, Smyth MJ, et al. IL-21 is produced by NKT cells and modulates NKT cell activation and cytokine production. J Immunol. 2007;178(5):2827\u201334. https:\/\/doi.org\/10.4049\/jimmunol.178.5.2827.","journal-title":"J Immunol"},{"issue":"1","key":"1031_CR7","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1479-7364-5-1-30","volume":"5","author":"C Brocker","year":"2010","unstructured":"Brocker C, Thompson D, Matsumoto A, Nebert DW, Vasiliou V. Evolutionary divergence and functions of the human interleukin (IL) gene family. Human Genomics. 2010;5(1):30\u201355.","journal-title":"Human Genomics"},{"issue":"4","key":"1031_CR8","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.immuni.2019.03.028","volume":"50","author":"WJ Leonard","year":"2019","unstructured":"Leonard WJ, Lin JX, O'Shea JJ. The \u03b3(c) family of cytokines: basic biology to therapeutic ramifications. Immunity. 2019;50(4):832\u201350. https:\/\/doi.org\/10.1016\/j.immuni.2019.03.028.","journal-title":"Immunity."},{"key":"1031_CR9","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.coi.2015.02.010","volume":"34","author":"SG Tangye","year":"2015","unstructured":"Tangye SG. Advances in IL-21 biology\u2014enhancing our understanding of human disease. Curr Opin Immunol. 2015;34:107\u201315. https:\/\/doi.org\/10.1016\/j.coi.2015.02.010.","journal-title":"Curr Opin Immunol"},{"issue":"1","key":"1031_CR10","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1084\/jem.20041057","volume":"201","author":"R Zeng","year":"2005","unstructured":"Zeng R, Spolski R, Finkelstein SE, Oh S, Kovanen PE, Hinrichs CS, et al. Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. J Exp Med. 2005;201(1):139\u201348.","journal-title":"J Exp Med"},{"issue":"8","key":"1031_CR11","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1002\/ibd.20923","volume":"15","author":"Z Liu","year":"2009","unstructured":"Liu Z, Yang L, Cui Y, Wang X, Guo C, Huang Z, et al. Il-21 enhances NK cell activation and cytolytic activity and induces Th17 cell differentiation in inflammatory bowel disease. Inflamm Bowel Dis. 2009;15(8):1133\u201344.","journal-title":"Inflamm Bowel Dis"},{"issue":"6","key":"1031_CR12","doi-asserted-by":"publisher","first-page":"e20191804","DOI":"10.1084\/jem.20191804","volume":"217","author":"V Beziat","year":"2020","unstructured":"Beziat V, Tavernier SJ, Chen YH, Ma CS, Materna M, Laurence A, et al. Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome. J Exp Med. 2020;217(6):e20191804. https:\/\/doi.org\/10.1084\/jem.20191804.","journal-title":"J Exp Med."},{"issue":"5","key":"1031_CR13","doi-asserted-by":"publisher","first-page":"e1003362","DOI":"10.1371\/journal.ppat.1003362","volume":"9","author":"I Schmitz","year":"2013","unstructured":"Schmitz I, Schneider C, Frohlich A, Frebel H, Christ D, Leonard WJ, et al. IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection. PLoS Pathog. 2013;9(5):e1003362. https:\/\/doi.org\/10.1371\/journal.ppat.1003362.","journal-title":"PLoS Pathog"},{"issue":"3","key":"1031_CR14","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.4049\/jimmunol.181.3.1767","volume":"181","author":"DT Avery","year":"2008","unstructured":"Avery DT, Bryant VL, Ma CS, de Waal MR, Tangye SG. IL-21-induced isotype switching to IgG and IgA by human naive B cells is differentially regulated by IL-4. J Immunol. 2008;181(3):1767\u201379.","journal-title":"J Immunol"},{"issue":"12","key":"1031_CR15","doi-asserted-by":"publisher","first-page":"7867","DOI":"10.4049\/jimmunol.175.12.7867","volume":"175","author":"R Ettinger","year":"2005","unstructured":"Ettinger R, Sims GP, Fairhurst A-M, Robbins R, da Silva YS, Spolski R, et al. IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells. J Immunol. 2005;175(12):7867\u201379.","journal-title":"J Immunol"},{"issue":"9","key":"1031_CR16","doi-asserted-by":"publisher","first-page":"5886","DOI":"10.4049\/jimmunol.179.9.5886","volume":"179","author":"S Kuchen","year":"2007","unstructured":"Kuchen S, Robbins R, Sims GP, Sheng C, Phillips TM, Lipsky PE, et al. Essential role of IL-21 in B cell activation, expansion, and plasma cell generation during CD4+ T cell-B cell collaboration. J Immunol. 2007;179(9):5886\u201396.","journal-title":"J Immunol"},{"issue":"8","key":"1031_CR17","doi-asserted-by":"publisher","first-page":"5236","DOI":"10.4049\/jimmunol.177.8.5236","volume":"177","author":"KL Good","year":"2006","unstructured":"Good KL, Bryant VL, Tangye SG. Kinetics of human B cell behavior and amplification of proliferative responses following stimulation with IL-21. J Immunol. 2006;177(8):5236\u201347. https:\/\/doi.org\/10.4049\/jimmunol.177.8.5236.","journal-title":"J Immunol"},{"issue":"12","key":"1031_CR18","doi-asserted-by":"publisher","first-page":"8180","DOI":"10.4049\/jimmunol.179.12.8180","volume":"179","author":"VL Bryant","year":"2007","unstructured":"Bryant VL, Ma CS, Avery DT, Li Y, Good KL, Corcoran LM, et al. Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells. J Immunol. 2007;179(12):8180\u201390. https:\/\/doi.org\/10.4049\/jimmunol.179.12.8180.","journal-title":"J Immunol"},{"issue":"8","key":"1031_CR19","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/icb.2009.64","volume":"87","author":"CS Ma","year":"2009","unstructured":"Ma CS, Suryani S, Avery DT, Chan A, Nanan R, Santner-Nanan B, et al. Early commitment of naive human CD4(+) T cells to the T follicular helper (T(FH)) cell lineage is induced by IL-12. Immunol Cell Biol. 2009;87(8):590\u2013600. https:\/\/doi.org\/10.1038\/icb.2009.64.","journal-title":"Immunol Cell Biol"},{"issue":"6","key":"1031_CR20","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1016\/j.jaci.2014.02.034","volume":"133","author":"E Salzer","year":"2014","unstructured":"Salzer E, Kansu A, Sic H, M\u00e1jek P, Ikincio\u011fullari A, Dogu FE, et al. Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency. J Allergy Clin Immunol. 2014;133(6):1651\u20139.e12. https:\/\/doi.org\/10.1016\/j.jaci.2014.02.034.","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"1031_CR21","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1097\/MOP.0000000000000160","volume":"26","author":"D Kotlarz","year":"2014","unstructured":"Kotlarz D, Zietara N, Milner JD, Klein C. Human IL-21 and IL-21R deficiencies: two novel entities of primary immunodeficiency. Curr Opin Pediatr. 2014;26(6):704\u201312.","journal-title":"Curr Opin Pediatr"},{"issue":"3","key":"1031_CR22","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1084\/jem.20111229","volume":"210","author":"D Kotlarz","year":"2013","unstructured":"Kotlarz D, Zietara N, Uzel G, Weidemann T, Braun CJ, Diestelhorst J, et al. Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome. J Exp Med. 2013;210(3):433\u201343. https:\/\/doi.org\/10.1084\/jem.20111229.","journal-title":"J Exp Med"},{"issue":"6","key":"1031_CR23","doi-asserted-by":"publisher","first-page":"e216","DOI":"10.3324\/haematol.2014.120980","volume":"100","author":"B Erman","year":"2015","unstructured":"Erman B, Bilic I, Hirschmugl T, Salzer E, Cagdas D, Esenboga S, et al. Combined immunodeficiency with CD4 lymphopenia and sclerosing cholangitis caused by a novel loss-of-function mutation affecting IL21R. Haematologica. 2015;100(6):e216\u20139. https:\/\/doi.org\/10.3324\/haematol.2014.120980.","journal-title":"Haematologica."},{"issue":"2","key":"1031_CR24","doi-asserted-by":"publisher","first-page":"e72","DOI":"10.3324\/haematol.2014.112508","volume":"100","author":"P Stepensky","year":"2015","unstructured":"Stepensky P, Keller B, Abuzaitoun O, Shaag A, Yaacov B, Unger S, et al. Extending the clinical and immunological phenotype of human interleukin-21 receptor deficiency. Haematologica. 2015;100(2):e72\u20136. https:\/\/doi.org\/10.3324\/haematol.2014.112508.","journal-title":"Haematologica."},{"issue":"2","key":"1031_CR25","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.jaci.2013.05.029","volume":"132","author":"ML Ives","year":"2013","unstructured":"Ives ML, Ma CS, Palendira U, Chan A, Bustamante J, Boisson-Dupuis S, et al. Signal transducer and activator of transcription 3 (STAT3) mutations underlying autosomal dominant hyper-IgE syndrome impair human CD8(+) T-cell memory formation and function. J Allergy Clin Immunol. 2013;132(2):400\u201311 e9. https:\/\/doi.org\/10.1016\/j.jaci.2013.05.029.","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"1031_CR26","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1016\/j.jaci.2015.05.036","volume":"136","author":"CS Ma","year":"2015","unstructured":"Ma CS, Wong N, Rao G, Avery DT, Torpy J, Hambridge T, et al. Monogenic mutations differentially affect the quantity and quality of T follicular helper cells in patients with human primary immunodeficiencies. J Allergy Clin Immunol. 2015;136(4):993\u20131006 e1. https:\/\/doi.org\/10.1016\/j.jaci.2015.05.036.","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"1031_CR27","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1084\/jem.20141992","volume":"212","author":"RP Wilson","year":"2015","unstructured":"Wilson RP, Ives ML, Rao G, Lau A, Payne K, Kobayashi M, et al. STAT3 is a critical cell-intrinsic regulator of human unconventional T cell numbers and function. J Exp Med. 2015;212(6):855\u201364. https:\/\/doi.org\/10.1084\/jem.20141992.","journal-title":"J Exp Med"},{"key":"1031_CR28","doi-asserted-by":"publisher","unstructured":"B\u00e9ziat V, Li J, Lin JX, Ma CS, Li P, Bousfiha A, et al. A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity. Sci Immunol. 2018;3(24). https:\/\/doi.org\/10.1126\/sciimmunol.aat4956.","DOI":"10.1126\/sciimmunol.aat4956"},{"issue":"24","key":"1031_CR29","doi-asserted-by":"publisher","first-page":"3940","DOI":"10.1182\/blood-2013-06-506865","volume":"122","author":"LJ Berglund","year":"2013","unstructured":"Berglund LJ, Avery DT, Ma CS, Moens L, Deenick EK, Bustamante J, et al. IL-21 signalling via STAT3 primes human naive B cells to respond to IL-2 to enhance their differentiation into plasmablasts. Blood. 2013;122(24):3940\u201350. https:\/\/doi.org\/10.1182\/blood-2013-06-506865.","journal-title":"Blood."},{"issue":"8","key":"1031_CR30","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1002\/cyto.a.24018","volume":"97","author":"K Payne","year":"2020","unstructured":"Payne K, Li W, Salomon R, Ma CS. OMIP-063: 28-color flow cytometry panel for broad human immunophenotyping. Cytometry A. 2020;97(8):777\u201381. https:\/\/doi.org\/10.1002\/cyto.a.24018.","journal-title":"Cytometry A"},{"issue":"1","key":"1031_CR31","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.immuni.2010.12.012","volume":"34","author":"R Morita","year":"2011","unstructured":"Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, et al. Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity. 2011;34(1):108\u201321. https:\/\/doi.org\/10.1016\/j.immuni.2010.12.012.","journal-title":"Immunity."},{"issue":"1","key":"1031_CR32","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1084\/jem.20091706","volume":"207","author":"DT Avery","year":"2010","unstructured":"Avery DT, Deenick EK, Ma CS, Suryani S, Simpson N, Chew GY, et al. B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans. J Exp Med. 2010;207(1):155\u201371. https:\/\/doi.org\/10.1084\/jem.20091706.","journal-title":"J Exp Med"},{"issue":"12","key":"1031_CR33","doi-asserted-by":"publisher","first-page":"2739","DOI":"10.1084\/jem.20130323","volume":"210","author":"EK Deenick","year":"2013","unstructured":"Deenick EK, Avery DT, Chan A, Berglund LJ, Ives ML, Moens L, et al. Naive and memory human B cells have distinct requirements for STAT3 activation to differentiate into antibody-secreting plasma cells. J Exp Med. 2013;210(12):2739\u201353. https:\/\/doi.org\/10.1084\/jem.20130323.","journal-title":"J Exp Med"},{"issue":"8","key":"1031_CR34","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1084\/jem.20151467","volume":"213","author":"CS Ma","year":"2016","unstructured":"Ma CS, Wong N, Rao G, Nguyen A, Avery DT, Payne K, et al. Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4+ T cells into distinct effector subsets. J Exp Med. 2016;213(8):1589\u2013608. https:\/\/doi.org\/10.1084\/jem.20151467.","journal-title":"J Exp Med"},{"key":"1031_CR35","doi-asserted-by":"publisher","first-page":"5360","DOI":"10.1038\/ncomms6360","volume":"5","author":"KL Willmann","year":"2014","unstructured":"Willmann KL, Klaver S, Do\u011fu F, Santos-Valente E, Garncarz W, Bilic I, et al. Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity. Nat Commun. 2014;5:5360.","journal-title":"Nat Commun"},{"key":"1031_CR36","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.3389\/fimmu.2018.02239","volume":"9","author":"L Israel","year":"2018","unstructured":"Israel L, Mellett M. Clinical and genetic heterogeneity of CARD14 mutations in psoriatic skin disease. Front Immunol. 2018;9:2239. https:\/\/doi.org\/10.3389\/fimmu.2018.02239.","journal-title":"Front Immunol"},{"issue":"12","key":"1031_CR37","doi-asserted-by":"publisher","first-page":"9454","DOI":"10.1074\/jbc.M111.311084","volume":"287","author":"OJ Hamming","year":"2012","unstructured":"Hamming OJ, Kang L, Svensson A, Karlsen JL, Rahbek-Nielsen H, Paludan SR, et al. Crystal structure of interleukin-21 receptor (IL-21R) bound to IL-21 reveals that sugar chain interacting with WSXWS motif is integral part of IL-21R. J Biol Chem. 2012;287(12):9454\u201360. https:\/\/doi.org\/10.1074\/jbc.M111.311084.","journal-title":"J Biol Chem"},{"issue":"6","key":"1031_CR38","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gene.2015.22","volume":"16","author":"P Siupka","year":"2015","unstructured":"Siupka P, Hamming OT, Kang L, Gad HH, Hartmann R. A conserved sugar bridge connected to the WSXWS motif has an important role for transport of IL-21R to the plasma membrane. Genes Immun. 2015;16(6):405\u201313. https:\/\/doi.org\/10.1038\/gene.2015.22.","journal-title":"Genes Immun"},{"issue":"10","key":"1031_CR39","doi-asserted-by":"publisher","first-page":"4135","DOI":"10.1182\/blood-2006-10-054973","volume":"109","author":"R Zeng","year":"2007","unstructured":"Zeng R, Spolski R, Casas E, Zhu W, Levy DE, Leonard WJ. The molecular basis of IL-21-mediated proliferation. Blood. 2007;109(10):4135\u201342.","journal-title":"Blood."},{"issue":"1","key":"1031_CR40","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1007\/s10875-019-00737-x","volume":"40","author":"SG Tangye","year":"2020","unstructured":"Tangye SG, Al-Herz W, Bousfiha A, Chatila T, Cunningham-Rundles C, Etzioni A, et al. Human inborn errors of immunity: 2019 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2020;40(1):24\u201364. https:\/\/doi.org\/10.1007\/s10875-019-00737-x.","journal-title":"J Clin Immunol"},{"issue":"10","key":"1031_CR41","doi-asserted-by":"publisher","first-page":"O656","DOI":"10.1111\/1469-0691.12573","volume":"20","author":"C Bodemer","year":"2014","unstructured":"Bodemer C, Sauvage V, Mahlaoui N, Cheval J, Couderc T, Leclerc-Mercier S, et al. Live rubella virus vaccine long-term persistence as an antigenic trigger of cutaneous granulomas in patients with primary immunodeficiency. Clin Microbiol Infect. 2014;20(10):O656\u201363. https:\/\/doi.org\/10.1111\/1469-0691.12573.","journal-title":"Clin Microbiol Infect"},{"issue":"4","key":"1031_CR42","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.4049\/jimmunol.172.4.2048","volume":"172","author":"J Brady","year":"2004","unstructured":"Brady J, Hayakawa Y, Smyth MJ, Nutt SL. IL-21 induces the functional maturation of murine NK cells. J Immunol. 2004;172(4):2048\u201358. https:\/\/doi.org\/10.4049\/jimmunol.172.4.2048.","journal-title":"J Immunol"},{"issue":"19","key":"1031_CR43","doi-asserted-by":"publisher","first-page":"3865","DOI":"10.1182\/blood-2010-04-282301","volume":"116","author":"S Lopez-Verg\u00e8s","year":"2010","unstructured":"Lopez-Verg\u00e8s S, Milush JM, Pandey S, York VA, Arakawa-Hoyt J, Pircher H, et al. CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood. 2010;116(19):3865\u201374. https:\/\/doi.org\/10.1182\/blood-2010-04-282301.","journal-title":"Blood."},{"issue":"5838","key":"1031_CR44","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1126\/science.1142963","volume":"317","author":"J-L Casanova","year":"2007","unstructured":"Casanova J-L, Abel L. Primary immunodeficiencies: a field in its infancy. Science. 2007;317(5838):617\u20139.","journal-title":"Science."},{"issue":"1","key":"1031_CR45","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.jaci.2012.04.029","volume":"130","author":"CM Roifman","year":"2012","unstructured":"Roifman CM, Somech R, Kavadas F, Pires L, Nahum A, Dalal I, et al. Defining combined immunodeficiency. J Allergy Clin Immunol. 2012;130(1):177\u201383.","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"1031_CR46","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1097\/01.md.0000100046.06009.b0","volume":"82","author":"JA Winkelstein","year":"2003","unstructured":"Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, et al. The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. Medicine (Baltimore). 2003;82(6):373\u201384. https:\/\/doi.org\/10.1097\/01.md.0000100046.06009.b0.","journal-title":"Medicine (Baltimore)"},{"key":"1031_CR47","doi-asserted-by":"publisher","unstructured":"Tangye SG, Ma CS. Regulation of the germinal center and humoral immunity by interleukin-21. J Exp Med. 2020;217(1). https:\/\/doi.org\/10.1084\/jem.20191638.","DOI":"10.1084\/jem.20191638"},{"issue":"1","key":"1031_CR48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4049\/jimmunol.167.1.1","volume":"167","author":"H Asao","year":"2001","unstructured":"Asao H, Okuyama C, Kumaki S, Ishii N, Tsuchiya S, Foster D, et al. Cutting edge: the common \u03b3-chain is an indispensable subunit of the IL-21 receptor complex. J Immunol. 2001;167(1):1\u20135. https:\/\/doi.org\/10.4049\/jimmunol.167.1.1.","journal-title":"J Immunol"},{"key":"1031_CR49","doi-asserted-by":"publisher","unstructured":"Frey-Jakobs S, Hartberger JM, Fliegauf M, Bossen C, Wehmeyer ML, Neubauer JC, et al. ZNF341 controls STAT3 expression and thereby immunocompetence. Sci Immunol. 2018;3(24). https:\/\/doi.org\/10.1126\/sciimmunol.aat4941.","DOI":"10.1126\/sciimmunol.aat4941"},{"issue":"7157","key":"1031_CR50","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1038\/nature06096","volume":"448","author":"Y Minegishi","year":"2007","unstructured":"Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T, et al. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature. 2007;448(7157):1058\u201362. https:\/\/doi.org\/10.1038\/nature06096.","journal-title":"Nature."},{"issue":"7214","key":"1031_CR51","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/nature07345","volume":"455","author":"H Qi","year":"2008","unstructured":"Qi H, Cannons JL, Klauschen F, Schwartzberg PL, Germain RN. SAP-controlled T-B cell interactions underlie germinal centre formation. Nature. 2008;455(7214):764\u20139.","journal-title":"Nature."},{"issue":"7188","key":"1031_CR52","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/nature06764","volume":"452","author":"JD Milner","year":"2008","unstructured":"Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, et al. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature. 2008;452(7188):773\u20136.","journal-title":"Nature."},{"key":"1031_CR53","doi-asserted-by":"publisher","unstructured":"Mart\u00ednez-Barricarte R, Markle JG, Ma CS, Deenick EK, Ram\u00edrez-Alejo N, Mele F, et al. Human IFN-\u03b3 immunity to mycobacteria is governed by both IL-12 and IL-23. Sci Immunol. 2018;3(30). https:\/\/doi.org\/10.1126\/sciimmunol.aau6759.","DOI":"10.1126\/sciimmunol.aau6759"},{"issue":"5598","key":"1031_CR54","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1126\/science.1077002","volume":"298","author":"K Ozaki","year":"2002","unstructured":"Ozaki K, Spolski R, Feng CG, Qi C-F, Cheng J, Sher A, et al. A critical role for IL-21 in regulating immunoglobulin production. Science. 2002;298(5598):1630\u20134. https:\/\/doi.org\/10.1126\/science.1077002.","journal-title":"Science."},{"issue":"12","key":"1031_CR55","doi-asserted-by":"publisher","first-page":"8554","DOI":"10.4049\/jimmunol.179.12.8554","volume":"179","author":"T Kishida","year":"2007","unstructured":"Kishida T, Hiromura Y, Shin-Ya M, Asada H, Kuriyama H, Sugai M, et al. IL-21 induces inhibitor of differentiation 2 and leads to complete abrogation of anaphylaxis in mice. J Immunol. 2007;179(12):8554\u201361. https:\/\/doi.org\/10.4049\/jimmunol.179.12.8554.","journal-title":"J Immunol"},{"issue":"6","key":"1031_CR56","doi-asserted-by":"publisher","first-page":"2178","DOI":"10.1016\/j.jaci.2018.11.047","volume":"143","author":"L Tortola","year":"2019","unstructured":"Tortola L, Pawelski H, Sonar SS, Ampenberger F, Kurrer M, Kopf M. IL-21 promotes allergic airway inflammation by driving apoptosis of FoxP3(+) regulatory T cells. J Allergy Clin Immunol. 2019;143(6):2178\u201389.e5. https:\/\/doi.org\/10.1016\/j.jaci.2018.11.047.","journal-title":"J Allergy Clin Immunol"},{"issue":"1","key":"1031_CR57","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s10875-018-0581-0","volume":"39","author":"D Buchbinder","year":"2019","unstructured":"Buchbinder D, Hauck F, Albert MH, Rack A, Bakhtiar S, Shcherbina A, et al. Rubella virus-associated cutaneous granulomatous disease: a unique complication in immune-deficient patients, not limited to DNA repair disorders. J Clin Immunol. 2019;39(1):81\u20139. https:\/\/doi.org\/10.1007\/s10875-018-0581-0.","journal-title":"J Clin Immunol"},{"issue":"7","key":"1031_CR58","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1111\/jdv.15568","volume":"33","author":"S Leclerc-Mercier","year":"2019","unstructured":"Leclerc-Mercier S, Moshous D, Neven B, Mahlaoui N, Martin L, Pellier I, et al. Cutaneous granulomas with primary immunodeficiency in children: a report of 17 new patients and a review of the literature. J Eur Acad Dermatol Venereol. 2019;33(7):1412\u201320. https:\/\/doi.org\/10.1111\/jdv.15568.","journal-title":"J Eur Acad Dermatol Venereol"},{"issue":"6","key":"1031_CR59","doi-asserted-by":"publisher","first-page":"2238","DOI":"10.1016\/j.jaci.2018.12.1010","volume":"143","author":"F Ferrua","year":"2019","unstructured":"Ferrua F, Galimberti S, Courteille V, Slatter MA, Booth C, Moshous D, et al. Hematopoietic stem cell transplantation for CD40 ligand deficiency: results from an EBMT\/ESID-IEWP-SCETIDE-PIDTC study. J Allergy Clin Immunol. 2019;143(6):2238\u201353. https:\/\/doi.org\/10.1016\/j.jaci.2018.12.1010.","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"1031_CR60","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/bmt.2012.239","volume":"48","author":"R Olsson","year":"2013","unstructured":"Olsson R, Remberger M, Schaffer M, Berggren DM, Svahn BM, Mattsson J, et al. Graft failure in the modern era of allogeneic hematopoietic SCT. Bone Marrow Transplant. 2013;48(4):537\u201343. https:\/\/doi.org\/10.1038\/bmt.2012.239.","journal-title":"Bone Marrow Transplant"},{"issue":"5","key":"1031_CR61","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.jaci.2003.07.003","volume":"112","author":"WT Shearer","year":"2003","unstructured":"Shearer WT, Rosenblatt HM, Gelman RS, Oyomopito R, Plaeger S, Stiehm ER, et al. Lymphocyte subsets in healthy children from birth through 18 years of age: the pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clin Immunol. 2003;112(5):973\u201380. https:\/\/doi.org\/10.1016\/j.jaci.2003.07.003.","journal-title":"J Allergy Clin Immunol"}],"container-title":["Journal of Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-021-01031-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10875-021-01031-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-021-01031-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T09:01:19Z","timestamp":1744189279000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10875-021-01031-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,30]]},"references-count":61,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["1031"],"URL":"https:\/\/doi.org\/10.1007\/s10875-021-01031-5","relation":{},"ISSN":["0271-9142","1573-2592"],"issn-type":[{"value":"0271-9142","type":"print"},{"value":"1573-2592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,30]]},"assertion":[{"value":"7 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"This work is a review of recently reported genetic variants that represent novel inborn errors of immunity. No human research studies were performed in order to produce this review. Thus, no approvals by appropriate institutional review boards or human research ethics committees were required to undertake the preparation of this report.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable as this is a review of recently reported genetic variants.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"The authors consent to publish the content of this review. However, as noted above, as this is a review of recently reported genetic variants that represent novel inborn errors of immunity, we did not require consent to publish from participants.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Publish"}},{"value":"The authors declare that they have no conflict of interest.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"Not applicable","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data and Materials"}}]}}