{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:04:09Z","timestamp":1784865849436,"version":"3.55.0"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Germline CARD11 gain-of-function (GOF) mutations cause B cell Expansion with NF-\u03baB and T cell Anergy (BENTA) disease, whilst somatic GOF CARD11 mutations recur in diffuse large B cell lymphoma (DLBCL) and in up to 30% of the peripheral T cell lymphomas (PTCL) adult T cell leukemia\/lymphoma (ATL), cutaneous T cell lymphoma (CTCL) and Sezary Syndrome. Despite their frequent acquisition by PTCL, the T cell-intrinsic effects of CARD11 GOF mutations are poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we studied B and T lymphocytes in mice with a germline Nethyl-N-nitrosourea (ENU)-induced Card11<jats:sup>M365K<\/jats:sup> mutation identical to a mutation identified in DLBCL and modifying a conserved region of the CARD11 coiled-coil domain recurrently mutated in DLBCL and PTCL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>Our results demonstrate that CARD11.M365K is a GOF protein that increases B and T lymphocyte activation and proliferation following antigen receptor stimulation. Germline Card11<jats:sup>M365K<\/jats:sup> mutation was insufficient alone to cause B or T-lymphoma, but increased accumulation of germinal center (GC) B cells in unimmunized and immunized mice. Card11<jats:sup>M365K<\/jats:sup> mutation caused cell-intrinsic over-accumulation of activated T cells, T regulatory (T<jats:sub>REG<\/jats:sub>), T follicular (T<jats:sub>FH<\/jats:sub>) and T follicular regulatory (T<jats:sub>FR<\/jats:sub>) cells expressing increased levels of ICOS, CTLA-4 and PD-1 checkpoint molecules. Our results reveal CARD11 as an important, cell-autonomous positive regulator of T<jats:sub>FH<\/jats:sub>, T<jats:sub>REG<\/jats:sub> and T<jats:sub>FR<\/jats:sub> cells. They highlight T cell-intrinsic effects of a GOF mutation in the CARD11 gene, which is recurrently mutated in T cell malignancies that are often aggressive and associated with variable clinical outcomes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1095257","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T06:00:37Z","timestamp":1678168837000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["CARD11 gain-of-function mutation drives cell-autonomous accumulation of PD-1+ ICOShigh activated T cells, T-follicular, T-regulatory and T-follicular regulatory cells"],"prefix":"10.3389","volume":"14","author":[{"given":"Etienne","family":"Masle-Farquhar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh","family":"Jeelall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Bier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elissa K.","family":"Deenick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Brink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Horikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher Carl","family":"Goodnow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010512200","article-title":"CARD11 and CARD14 are novel caspase recruitment domain (CARD)\/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa b","volume":"276","author":"Bertin","year":"2001","journal-title":"J Biol Chem"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.09.014","article-title":"Phosphorylation of the CARMA1 linker controls NF-kappaB activation","volume":"23","author":"Sommer","year":"2005","journal-title":"Immunity"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.10.007","article-title":"Phosphorylation of CARMA1 plays a critical role in T cell receptor-mediated NF-kappaB activation","volume":"23","author":"Matsumoto","year":"2005","journal-title":"Immunity"},{"key":"B4","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/nri1944","article-title":"The CARMA1 signalosome links the signalling machinery of adaptive and innate immunity in lymphocytes","volume":"6","author":"Rawlings","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1111\/j.1600-065X.2008.00749.x","article-title":"CARMA1-mediated NF-kappaB and JNK activation in lymphocytes","volume":"228","author":"Blonska","year":"2009","journal-title":"Immunol Rev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02414-0","article-title":"Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappaB activation","volume":"496","author":"Gaide","year":"2001","journal-title":"FEBS Lett"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103824200","article-title":"Bimp1, a MAGUK family member linking protein kinase c activation to Bcl10-mediated NF-kappaB induction","volume":"276","author":"McAllister-Lucas","year":"2001","journal-title":"J Biol Chem"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.08.032","article-title":"Structural architecture of the CARMA1\/Bcl10\/MALT1 signalosome: Nucleation-induced filamentous assembly","volume":"51","author":"Qiao","year":"2013","journal-title":"Mol Cell"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00491-3","article-title":"Requirement for CARMA1 in antigen receptor-induced NF-kappa b activation and lymphocyte proliferation","volume":"13","author":"Egawa","year":"2003","journal-title":"Curr Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00141-9","article-title":"Identifying the MAGUK protein carma-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesis","volume":"18","author":"Jun","year":"2003","journal-title":"Immunity"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00458-5","article-title":"Mice lacking the CARD of CARMA1 exhibit defective b lymphocyte development and impaired proliferation of their b and T lymphocytes","volume":"13","author":"Newton","year":"2003","journal-title":"Curr Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00148-1","article-title":"The MAGUK family protein CARD11 is essential for lymphocyte activation","volume":"18","author":"Hara","year":"2003","journal-title":"Immunity"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000051","article-title":"Commitment to the regulatory T cell lineage requires CARMA1 in the thymus but not in the periphery","volume":"7","author":"Barnes","year":"2009","journal-title":"PloS Biol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900498","article-title":"CARMA1 controls an early checkpoint in the thymic development of FoxP3+ regulatory T cells","volume":"182","author":"Molinero","year":"2009","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.095190","article-title":"CARMA1 regulation of regulatory T cell development involves modulation of interleukin-2 receptor signaling","volume":"285","author":"Lee","year":"2010","journal-title":"J Biol Chem"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1016\/j.jaci.2010.12.1081","article-title":"Decreased T-cell receptor signaling through CARD11 differentially compromises forkhead box protein 3-positive regulatory versus T(H)2 effector cells to cause allergy","volume":"127","author":"Altin","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3898","article-title":"Germline hypomorphic CARD11 mutations in severe atopic disease","volume":"49","author":"Ma","year":"2017","journal-title":"Nat Genet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.1016\/j.jaci.2017.06.047","article-title":"Combined immunodeficiency and atopy caused by a dominant negative mutation in caspase activation and recruitment domain family member 11 (CARD11)","volume":"141","author":"Dadi","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.08.013","article-title":"Hypomorphic caspase activation and recruitment domain 11 (CARD11) mutations associated with diverse immunologic phenotypes with or without atopic disease","volume":"143","author":"Dorjbal","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1016\/j.jaci.2013.02.012","article-title":"Whole-exome sequencing links caspase recruitment domain 11 (CARD11) inactivation to severe combined immunodeficiency","volume":"131","author":"Greil","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.jaci.2012.11.050","article-title":"Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects","volume":"131","author":"Stepensky","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00913","article-title":"Intrinsic plasma cell differentiation defects in b cell expansion with NF-kappaB and T cell anergy patient b cells","volume":"8","author":"Arjunaraja","year":"2017","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000217","article-title":"Gain-of-function mutations and immunodeficiency: at a loss for proper tuning of lymphocyte signaling","volume":"15","author":"Arjunaraja","year":"2015","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1007\/s10875-014-0106-4","article-title":"Germline CARD11 mutation in a patient with severe congenital b cell lymphocytosis","volume":"35","author":"Brohl","year":"2015","journal-title":"J Clin Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.jaci.2015.03.008","article-title":"Mild b-cell lymphocytosis in patients with a CARD11 C49Y mutation","volume":"136","author":"Buchbinder","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02944","article-title":"A unique heterozygous CARD11 mutation combines pathogenic features of both gain- and loss-of-Function patients in a four-generation family","volume":"9","author":"Desjardins","year":"2018","journal-title":"Front Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01049","article-title":"Clinical, immunological, and molecular findings in four cases of b cell expansion with NF-kappaB and T cell anergy disease for the first time from India","volume":"9","author":"Gupta","year":"2018","journal-title":"Front Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.clim.2016.02.002","article-title":"Constant b cell lymphocytosis since early age in a patient with CARD11 mutation: A 20-year follow-up","volume":"165","author":"Outinen","year":"2016","journal-title":"Clin Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120831","article-title":"Congenital b cell lymphocytosis explained by novel germline CARD11 mutations","volume":"209","author":"Snow","year":"2012","journal-title":"J Exp Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nature07968","article-title":"Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large b-cell lymphoma","volume":"459","author":"Compagno","year":"2009","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1126\/science.1153629","article-title":"Oncogenic CARD11 mutations in human diffuse large b cell lymphoma","volume":"319","author":"Lenz","year":"2008","journal-title":"Science"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/35000501","article-title":"Distinct types of diffuse large b-cell lymphoma identified by gene expression profiling","volume":"403","author":"Alizadeh","year":"2000","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.12.1861","article-title":"Constitutive nuclear factor kappaB activity is required for survival of activated b cell-like diffuse large b cell lymphoma cells","volume":"194","author":"Davis","year":"2001","journal-title":"J Exp Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nature04687","article-title":"A loss-of-function RNA interference screen for molecular targets in cancer","volume":"441","author":"Ngo","year":"2006","journal-title":"Nature"},{"key":"B35","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/nature08638","article-title":"Chronic active b-cell-receptor signalling in diffuse large b-cell lymphoma","volume":"463","author":"Davis","year":"2010","journal-title":"Nature"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1021\/bi101052d","article-title":"Oncogenic CARD11 mutations induce hyperactive signaling by disrupting autoinhibition by the PKC-responsive inhibitory domain","volume":"49","author":"Lamason","year":"2010","journal-title":"Biochemistry"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.683714","article-title":"Cooperative control of caspase recruitment domain-containing protein 11 (CARD11) signaling by an unusual array of redundant repressive elements","volume":"291","author":"Jattani","year":"2016","journal-title":"J Biol Chem"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3415","article-title":"Integrated molecular analysis of adult T cell leukemia\/lymphoma","volume":"47","author":"Kataoka","year":"2015","journal-title":"Nat Genet"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-01-761874","article-title":"Prognostic relevance of integrated genetic profiling in adult T-cell leukemia\/lymphoma","volume":"131","author":"Kataoka","year":"2018","journal-title":"Blood"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V50.3.481.481","article-title":"Adult T-cell leukemia: clinical and hematologic features of 16 cases","volume":"50","author":"Uchiyama","year":"1977","journal-title":"Blood"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/science.6760397","article-title":"Natural antibodies to human retrovirus HTLV in a cluster of Japanese patients with adult T cell leukemia","volume":"215","author":"Robert-Guroff","year":"1982","journal-title":"Science"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.12.3618","article-title":"Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA","volume":"80","author":"Seiki","year":"1983","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3356","article-title":"Genomic landscape of cutaneous T cell lymphoma","volume":"47","author":"Choi","year":"2015","journal-title":"Nat Genet"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3442","article-title":"The mutational landscape of cutaneous T cell lymphoma and sezary syndrome","volume":"47","author":"da Silva Almeida","year":"2015","journal-title":"Nat Genet"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.03.024","article-title":"Identification of gene mutations and fusion genes in patients with sezary syndrome","volume":"136","author":"Prasad","year":"2016","journal-title":"J Invest Dermatol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3444","article-title":"Genomic profiling of sezary syndrome identifies alterations of key T cell signaling and differentiation genes","volume":"47","author":"Wang","year":"2015","journal-title":"Nat Genet"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-632489","article-title":"Treatment and survival among 1594 patients with ATL","volume":"126","author":"Katsuya","year":"2015","journal-title":"Blood"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.7142","article-title":"Cutaneous lymphoma international consortium study of outcome in advanced stages of mycosis fungoides and sezary syndrome: Effect of specific prognostic markers on survival and development of a prognostic model","volume":"33","author":"Scarisbrick","year":"2015","journal-title":"J Clin Oncol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/j.1349-7006.2007.00646.x","article-title":"Adult T-cell leukemia\/lymphoma cells from blood and skin tumors express cytotoxic T lymphocyte-associated antigen-4 and Foxp3 but lack suppressor activity toward autologous CD8+ T cells","volume":"99","author":"Shimauchi","year":"2008","journal-title":"Cancer Sci"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111992","article-title":"Interleukin-2 receptor (Tac antigen) expressed on adult T cell leukemia cells","volume":"76","author":"Uchiyama","year":"1985","journal-title":"J Clin Invest."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/ng.892","article-title":"Analysis of the coding genome of diffuse large b-cell lymphoma","volume":"43","author":"Pasqualucci","year":"2011","journal-title":"Nat Genet"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1507459112","article-title":"Lymphomagenic CARD11\/BCL10\/MALT1 signaling drives malignant b-cell proliferation via cooperative NF-kappaB and JNK activation","volume":"112","author":"Knies","year":"2015","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180230","article-title":"Activated CARD11 accelerates germinal center kinetics, promoting mTORC1 and terminal differentiation","volume":"215","author":"Wray-Dutra","year":"2018","journal-title":"J Exp Med"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aaw5618","article-title":"Pathogenic CARD11 mutations affect b cell development and differentiation through a noncanonical pathway","volume":"4","author":"Wei","year":"2019","journal-title":"Sci Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.10.015","article-title":"Multiplexed functional assessment of genetic variants in CARD11","volume":"107","author":"Meitlis","year":"2020","journal-title":"Am J Hum Genet"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3428","article-title":"The genomic landscape of adult T cell leukemia\/lymphoma","volume":"47","author":"Vicente","year":"2015","journal-title":"Nat Genet"},{"key":"B57","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1182\/blood-2015-06-644948","article-title":"Variegated RHOA mutations in adult T-cell leukemia\/lymphoma","volume":"127","author":"Nagata","year":"2016","journal-title":"Blood"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13303","article-title":"Genetic alterations in adult T-cell leukemia\/lymphoma","volume":"108","author":"Kogure","year":"2017","journal-title":"Cancer Sci"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-504308","article-title":"PLCG1 mutations in cutaneous T-cell lymphomas","volume":"123","author":"Vaque","year":"2014","journal-title":"Blood"},{"key":"B60","doi-asserted-by":"publisher","first-page":"8470","DOI":"10.1038\/ncomms9470","article-title":"Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK-STAT pathway in sezary syndrome","volume":"6","author":"Kiel","year":"2015","journal-title":"Nat Commun"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3370","article-title":"Genomic analysis of mycosis fungoides and sezary syndrome identifies recurrent alterations in TNFR2","volume":"47","author":"Ungewickell","year":"2015","journal-title":"Nat Genet"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121343109","article-title":"Discovery and prioritization of somatic mutations in diffuse large b-cell lymphoma (DLBCL) by whole-exome sequencing","volume":"109","author":"Lohr","year":"2012","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205299110","article-title":"Genetic heterogeneity of diffuse large b-cell lymphoma","volume":"110","author":"Zhang","year":"2013","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B64","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.cell.2017.09.027","article-title":"Genetic and functional drivers of diffuse Large b cell lymphoma","volume":"171","author":"Reddy","year":"2017","journal-title":"Cell"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.01.029","article-title":"Lymphoma driver mutations in the pathogenic evolution of an iconic human autoantibody","volume":"180","author":"Singh","year":"2020","journal-title":"Cell"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2010.07.009","article-title":"A general chemical method to regulate protein stability in the mammalian central nervous system","volume":"17","author":"Iwamoto","year":"2010","journal-title":"Chem Biol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90030-G","article-title":"RAG-1-deficient mice have no mature b and T lymphocytes","volume":"68","author":"Mombaerts","year":"1992","journal-title":"Cell"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12268","article-title":"CARD11 is dispensable for homeostatic responses and suppressive activity of peripherally induced FOXP3(+) regulatory T cells","volume":"97","author":"Policheni","year":"2019","journal-title":"Immunol Cell Biol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2015.95","article-title":"A timeline demarcating two waves of clonal deletion and Foxp3 upregulation during thymocyte development","volume":"94","author":"Hu","year":"2016","journal-title":"Immunol Cell Biol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.01.003","article-title":"CCR7 controls thymus recirculation, but not production and emigration, of Foxp3(+) T cells","volume":"14","author":"Cowan","year":"2016","journal-title":"Cell Rep"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/nature24649","article-title":"PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis","volume":"552","author":"Wartewig","year":"2017","journal-title":"Nature"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1803181","article-title":"Rapid progression of adult T-cell leukemia-lymphoma after PD-1 inhibitor therapy","volume":"378","author":"Ratner","year":"2018","journal-title":"N Engl J Med"},{"key":"B73","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1056\/NEJMc1807852","article-title":"PD-1 inhibitor therapy in adult T-cell leukemia-lymphoma","volume":"379","author":"Ishitsuka","year":"2018","journal-title":"N Engl J Med"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.04999.x","article-title":"Expression of FoxP3, a key molecule in CD4CD25 regulatory T cells, in adult T-cell leukaemia\/lymphoma cells","volume":"126","author":"Karube","year":"2004","journal-title":"Br J Haematol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2005.00080.x","article-title":"Possible origin of adult T-cell leukemia\/lymphoma cells from human T lymphotropic virus type-1-infected regulatory T cells","volume":"96","author":"Kohno","year":"2005","journal-title":"Cancer Sci"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112744","article-title":"Human lymphoma mutations reveal CARD11 as the switch between self-antigen-induced b cell death or proliferation and autoantibody production","volume":"209","author":"Jeelall","year":"2012","journal-title":"J Exp Med"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.134.5.3070","article-title":"B cells in patients with X-linked agammaglobulinemia","volume":"134","author":"Conley","year":"1985","journal-title":"J Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)51014-6","article-title":"B-cell antigen receptor stimulation activates the human bruton\u2019s tyrosine kinase, which is deficient in X-linked agammaglobulinemia","volume":"269","author":"de Weers","year":"1994","journal-title":"J Biol Chem"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-016-0306-1","article-title":"NF-kappaB1 haploinsufficiency causing immunodeficiency and EBV-driven lymphoproliferation","volume":"36","author":"Boztug","year":"2016","journal-title":"J Clin Immunol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.jaci.2016.05.045","article-title":"Early and late b-cell developmental impairment in nuclear factor kappa b, subunit 1-mutated common variable immunodeficiency disease","volume":"139","author":"Lougaris","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90114-0","article-title":"Defective b cell development and function in btk-deficient mice","volume":"3","author":"Khan","year":"1995","journal-title":"Immunity"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90415-8","article-title":"Targeted disruption of the p50 subunit of NF-kappa b leads to multifocal defects in immune responses","volume":"80","author":"Sha","year":"1995","journal-title":"Cell"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.2.147","article-title":"Mice deficient in nuclear factor (NF)-kappa B\/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture","volume":"187","author":"Franzoso","year":"1998","journal-title":"J Exp Med"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.2.185","article-title":"Nuclear factor (NF)-kappa B2 (p100\/p52) is required for normal splenic microarchitecture and b cell-mediated immune responses","volume":"187","author":"Caamano","year":"1998","journal-title":"J Exp Med"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3746","article-title":"Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations","volume":"20","author":"Schubert","year":"2014","journal-title":"Nat Med"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061923","article-title":"Enhancement and suppression of signaling by the conserved tail of IgG memory-type b cell antigen receptors","volume":"204","author":"Horikawa","year":"2007","journal-title":"J Exp Med"},{"key":"B87","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/nature06253","article-title":"Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA","volume":"450","author":"Yu","year":"2007","journal-title":"Nature"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2426","article-title":"Follicular regulatory T cells expressing Foxp3 and bcl-6 suppress germinal center reactions","volume":"17","author":"Chung","year":"2011","journal-title":"Nat Med"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2425","article-title":"Foxp3+ follicular regulatory T cells control the germinal center response","volume":"17","author":"Linterman","year":"2011","journal-title":"Nat Med"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101328","article-title":"Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells","volume":"187","author":"Wollenberg","year":"2011","journal-title":"J Immunol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-02-698977","article-title":"Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell-derived lymphomas","volume":"128","author":"Vallois","year":"2016","journal-title":"Blood"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.121","article-title":"Personalized treatment of sezary syndrome by targeting a novel CTLA4:CD28 fusion","volume":"3","author":"Sekulic","year":"2015","journal-title":"Mol Genet Genomic Med"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-02-699843","article-title":"Candidate driver genes involved in genome maintenance and DNA repair in sezary syndrome","volume":"127","author":"Woollard","year":"2016","journal-title":"Blood"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh366","article-title":"Regulatory T cell-like activity of Foxp3+ adult T cell leukemia cells","volume":"18","author":"Chen","year":"2006","journal-title":"Int Immunol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-055145","article-title":"The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells","volume":"109","author":"de Leval","year":"2007","journal-title":"Blood"},{"key":"B96","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1097\/00000478-200103000-00015","article-title":"Peripheral T-cell lymphoma with follicular involvement and a CD4+\/bcl-6+ phenotype","volume":"25","author":"de Leval","year":"2001","journal-title":"Am J Surg Pathol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.133074","article-title":"A highly recurrent novel missense mutation in CD28 among angioimmunoblastic T-cell lymphoma patients","volume":"100","author":"Lee","year":"2015","journal-title":"Haematologica"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.357","article-title":"Recurrent activating mutations of CD28 in peripheral T-cell lymphomas","volume":"30","author":"Rohr","year":"2016","journal-title":"Leukemia"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2916","article-title":"A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma","volume":"46","author":"Yoo","year":"2014","journal-title":"Nat Genet"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2872","article-title":"Somatic RHOA mutation in angioimmunoblastic T cell lymphoma","volume":"46","author":"Sakata-Yanagimoto","year":"2014","journal-title":"Nat Genet"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2873","article-title":"Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas","volume":"46","author":"Palomero","year":"2014","journal-title":"Nat Genet"},{"key":"B102","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.ccell.2018.01.001","article-title":"RHOA G17V induces T follicular helper cell specification and promotes lymphomagenesis","volume":"33","author":"Cortes","year":"2018","journal-title":"Cancer Cell"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.2.774","article-title":"ICOS controls the pool size of effector-memory and regulatory T cells","volume":"180","author":"Burmeister","year":"2008","journal-title":"J Immunol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.12.006","article-title":"Regulatory T cells control antigen-specific expansion of tfh cell number and humoral immune responses via the coreceptor CTLA-4","volume":"41","author":"Wing","year":"2014","journal-title":"Immunity"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1292","article-title":"T Cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition","volume":"355","author":"Hui","year":"2017","journal-title":"Science"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.6.2031","article-title":"Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease","volume":"79","author":"Yoshida","year":"1982","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/312521a0","article-title":"Sequence and expression of transcripts of the human T-cell receptor beta-chain genes","volume":"312","author":"Yoshikai","year":"1984","journal-title":"Nature"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.12.8035-8044.1994","article-title":"Tax induces nuclear translocation of NF-kappa b through dissociation of cytoplasmic complexes containing p105 or p100 but does not induce degradation of I kappa b alpha\/MAD3","volume":"68","author":"Munoz","year":"1994","journal-title":"J Virol"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06900-11","article-title":"Distinct transformation tropism exhibited by human T lymphotropic virus type 1 (HTLV-1) and HTLV-2 is the result of postinfection T cell clonal expansion","volume":"86","author":"Kannian","year":"2012","journal-title":"J Virol"},{"key":"B110","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1471-2172-9-41","article-title":"The frequency of CD127low expressing CD4+CD25high T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy\/tropical spastic paraparesis","volume":"9","author":"Michaelsson","year":"2008","journal-title":"BMC Immunol"},{"key":"B111","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/1742-4690-9-46","article-title":"HTLV-1 modulates the frequency and phenotype of FoxP3+CD4+ T cells in virus-infected individuals","volume":"9","author":"Satou","year":"2012","journal-title":"Retrovirology"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.4558","article-title":"International peripheral T-cell and natural killer\/T-cell lymphoma study: pathology findings and clinical outcomes","volume":"26","author":"Vose","year":"2008","journal-title":"J Clin Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1095257\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T06:00:40Z","timestamp":1678168840000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1095257\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,7]]},"references-count":112,"alternative-id":["10.3389\/fimmu.2023.1095257"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1095257","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,7]]},"article-number":"1095257"}}