{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:30:09Z","timestamp":1791419409544,"version":"4.3.3"},"reference-count":105,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"91","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2024,1,12]]},"abstract":"<jats:p>\n                    Defective FAS (CD95\/Apo-1\/TNFRSF6) signaling causes autoimmune lymphoproliferative syndrome (ALPS). Hypergammaglobulinemia is a common feature in ALPS with\n                    <jats:italic>FAS<\/jats:italic>\n                    mutations (ALPS-FAS), but paradoxically, fewer conventional memory cells differentiate from FAS-expressing germinal center (GC) B cells. Resistance to FAS-induced apoptosis does not explain this phenotype. We tested the hypothesis that defective non-apoptotic FAS signaling may contribute to impaired B cell differentiation in ALPS. We analyzed secondary lymphoid organs of patients with ALPS-FAS and found low numbers of memory B cells, fewer GC B cells, and an expanded extrafollicular (EF) B cell response. Enhanced mTOR activity has been shown to favor EF versus GC fate decision, and we found enhanced PI3K\/mTOR and BCR signaling in ALPS-FAS splenic B cells. Modeling initial T-dependent B cell activation with CD40L in vitro, we showed that FAS competent cells with transient FAS ligation showed specifically decreased mTOR axis activation without apoptosis. Mechanistically, transient FAS engagement with involvement of caspase-8 induced nuclear exclusion of PTEN, leading to mTOR inhibition. In addition, FASL-dependent PTEN nuclear exclusion and mTOR modulation were defective in patients with ALPS-FAS. In the early phase of activation, FAS stimulation promoted expression of genes related to GC initiation at the expense of processes related to the EF response. Hence, our data suggest that non-apoptotic FAS signaling acts as molecular switch between EF versus GC fate decisions via regulation of the mTOR axis and transcription. The defect of this modulatory circuit may explain the observed hypergammaglobulinemia and low memory B cell numbers in ALPS.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.adj5948","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T13:58:21Z","timestamp":1705067901000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":26,"title":["Non-apoptotic FAS signaling controls mTOR activation and extrafollicular maturation in human B cells"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4050-2772","authenticated-orcid":true,"given":"Julian","family":"Staniek","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"Faculty of Biology, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5335-9515","authenticated-orcid":true,"given":"Tomas","family":"Kalina","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5389-9481","authenticated-orcid":true,"given":"Geoffroy","family":"Andrieux","sequence":"additional","affiliation":[{"name":"Institute of Medical Bioinformatics and Systems Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"German Cancer Consortium (DKTK), partner site Freiburg, and German Cancer Research Center (DKFZ), Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3670-0602","authenticated-orcid":true,"given":"Melanie","family":"Boerries","sequence":"additional","affiliation":[{"name":"Institute of Medical Bioinformatics and Systems Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"German Cancer Consortium (DKTK), partner site Freiburg, and German Cancer Research Center (DKFZ), Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7526-2803","authenticated-orcid":true,"given":"Iga","family":"Janowska","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-3766","authenticated-orcid":true,"given":"Manuel","family":"Fuentes","sequence":"additional","affiliation":[{"name":"Department of Medicine and General Cytometry Service-Nucleus, Proteomics Unit, CIBERONC CB16\/12\/00400, Cancer Research Center (IBMCC\/CSIC\/USAL\/IBSAL), Universidad de Salamanca, Salamanca, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2150-6898","authenticated-orcid":true,"given":"Paula","family":"D\u00edez","sequence":"additional","affiliation":[{"name":"Department of Medicine and General Cytometry Service-Nucleus, Proteomics Unit, CIBERONC CB16\/12\/00400, Cancer Research Center (IBMCC\/CSIC\/USAL\/IBSAL), Universidad de Salamanca, Salamanca, Spain."},{"name":"Department of Immunology, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5919-6306","authenticated-orcid":true,"given":"Marina","family":"Bakardjieva","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1059-3404","authenticated-orcid":true,"given":"Jitka","family":"Stancikova","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6894-1451","authenticated-orcid":true,"given":"Jan","family":"Raabe","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0518-2512","authenticated-orcid":true,"given":"Julika","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5896-6716","authenticated-orcid":true,"given":"Sabine","family":"Schwenk","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5779-0981","authenticated-orcid":true,"given":"Leonardo","family":"Arpesella","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Stuchly","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0352-2547","authenticated-orcid":true,"given":"Vladimir","family":"Benes","sequence":"additional","affiliation":[{"name":"Genomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0444-5587","authenticated-orcid":true,"given":"Rodrigo","family":"Garc\u00eda Valiente","sequence":"additional","affiliation":[{"name":"Department of Medicine and General Cytometry Service-Nucleus, Proteomics Unit, CIBERONC CB16\/12\/00400, Cancer Research Center (IBMCC\/CSIC\/USAL\/IBSAL), Universidad de Salamanca, Salamanca, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3676-7855","authenticated-orcid":true,"given":"Jonatan","family":"Fern\u00e1ndez Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Medicine and General Cytometry Service-Nucleus, Proteomics Unit, CIBERONC CB16\/12\/00400, Cancer Research Center (IBMCC\/CSIC\/USAL\/IBSAL), Universidad de Salamanca, Salamanca, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2632-1078","authenticated-orcid":true,"given":"Rita","family":"Carsetti","sequence":"additional","affiliation":[{"name":"B Cell Unit, Immunology Research Area, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0054-4732","authenticated-orcid":true,"given":"Eva","family":"Piano Mortari","sequence":"additional","affiliation":[{"name":"B Cell Unit, Immunology Research Area, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0133-1752","authenticated-orcid":true,"given":"Albert","family":"Catala","sequence":"additional","affiliation":[{"name":"Department of Hematology, Institut de Recerca Hospital Sant Joan de D\u00e9u Barcelona, Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9717-053X","authenticated-orcid":true,"given":"Oscar","family":"de la Calle","sequence":"additional","affiliation":[{"name":"Immunology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0855-2945","authenticated-orcid":true,"given":"Georgios","family":"Sogkas","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Neven","sequence":"additional","affiliation":[{"name":"Pediatric Hematology-Immunology and Rheumatology Department, University Hospital Necker-Enfants Malades, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7858-7866","authenticated-orcid":true,"given":"Fr\u00e9d\u00e9ric","family":"Rieux-Laucat","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7365-699X","authenticated-orcid":true,"given":"Aude","family":"Magerus","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5018-0466","authenticated-orcid":true,"given":"Olaf","family":"Neth","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Rheumatology and Immunology, Hospital Universitario Virgen del Rocio (HUVR), Instituto de Biomedicina de Sevilla (IBIS), Universidad de Sevilla\/CSIC, Red de Investigaci\u00f3n Traslacional en Infectolog\u00eda Pedi\u00e1trica RITIP, Sevilla, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9853-7903","authenticated-orcid":true,"given":"Peter","family":"Olbrich","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Rheumatology and Immunology, Hospital Universitario Virgen del Rocio (HUVR), Instituto de Biomedicina de Sevilla (IBIS), Universidad de Sevilla\/CSIC, Red de Investigaci\u00f3n Traslacional en Infectolog\u00eda Pedi\u00e1trica RITIP, Sevilla, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5542-9133","authenticated-orcid":true,"given":"Reinhard E.","family":"Voll","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3559-0018","authenticated-orcid":true,"given":"Laia","family":"Alsina","sequence":"additional","affiliation":[{"name":"Department of Hematology, Institut de Recerca Hospital Sant Joan de D\u00e9u Barcelona, Barcelona, Spain."},{"name":"Clinical Immunology and Primary Immunodeficiencies Unit, Department of Pediatric Allergy and Clinical Immunology, Hospital Sant Joan de D\u00e9u Barcelona, Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9586-8539","authenticated-orcid":true,"given":"Luis M.","family":"Allende","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6917-8980","authenticated-orcid":true,"given":"Luis I.","family":"Gonzalez-Granado","sequence":"additional","affiliation":[{"name":"Primary Immunodeficiencies Unit, Department of Pediatrics, Research Institute Hospital 12 Octubre (i+12), Madrid, Spain."},{"name":"School of Medicine, Complutense University, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"B\u00f6hler","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Thiel","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"Division of Rheumatology and Clinical Immunology, Medical University Graz, Graz, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7729-2759","authenticated-orcid":true,"given":"Nils","family":"Venhoff","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0184-1609","authenticated-orcid":true,"given":"Raquel","family":"Lorenzetti","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"Division of Rheumatology and Clinical Immunology, Medical University Graz, Graz, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-865X","authenticated-orcid":true,"given":"Klaus","family":"Warnatz","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"Department of Immunology, University Hospital Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6916-7544","authenticated-orcid":true,"given":"Susanne","family":"Unger","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5559-4980","authenticated-orcid":true,"given":"Maximilian","family":"Seidl","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Medical Center Freiburg, Freiburg, Germany."},{"name":"Institute of Pathology, Heinrich-Heine University and University Hospital of D\u00fcsseldorf, D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1135-0642","authenticated-orcid":true,"given":"Dirk","family":"Mielenz","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus Fiebiger Zentrum, Friedrich Alexander University Erlangen-N\u00fcrnberg, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9265-2721","authenticated-orcid":true,"given":"Stephan","family":"Ehl","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"CIBSS\u2014Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7031-0018","authenticated-orcid":true,"given":"Anne","family":"Rensing-Ehl","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-8116","authenticated-orcid":true,"given":"Cristian Roberto","family":"Smulski","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"Medical Physics Department, Centro At\u00f3mico Bariloche, Comisi\u00f3n Nacional de Energ\u00eda At\u00f3mica (CNEA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), San Carlos de Bariloche, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5153-6089","authenticated-orcid":true,"given":"Marta","family":"Rizzi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"CIBSS\u2014Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany."},{"name":"Division of Clinical and Experimental Immunology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7539157"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/356314a0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-02-553834"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.08.008"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.07.016"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00100-5"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20221346"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080840"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073924"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-04-642488"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.127885"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.07.001"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20202489"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200866"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.12.004"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02458"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abh0891"},{"key":"e_1_3_2_19_2","first-page":"402","article-title":"Age-associated B cells in autoimmune diseases","volume":"79","author":"Mouat I. C.","year":"2022","unstructured":"I. C. Mouat, E. Goldberg, M. S. Horwitz, Age-associated B cells in autoimmune diseases. Sci. Adv. 79, 402 (2022).","journal-title":"Sci. Adv."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010297"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05273-0"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.08.015"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.04.009"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3287"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2418"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.016"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00228"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1080\/10409238.2016.1215288"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.12.020"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01187-14"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI86504"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009131"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215039"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00814-z"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3175"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.04.031"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.01.001"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535483"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.16.9136"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1809"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001090"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2001390"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100898108"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13895"},{"key":"e_1_3_2_45_2","doi-asserted-by":"crossref","unstructured":"L. McInnes J. Healy Umap: Uniform manifold approximation and projection for dimension reduction. arXiv:1802.03426 [stat.ML] (2018).","DOI":"10.21105\/joss.00861"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201952"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132607"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.3.563"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-2-2"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.04.041"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192191"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0320(20010901)45:1<47::AID-CYTO1143>3.0.CO;2-A"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.703918"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060087"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030150"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.4.1428-1440.2003"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.4.447"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/40657"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.5.1557"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809136105"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.004"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.5b00474"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2016.05.005"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07290"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.11.040"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.4.631"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.370"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3978"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80294-9"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.3.1337"},{"key":"e_1_3_2_71_2","first-page":"5010","article-title":"Phosphorylation of the PTEN tail regulates protein stability and function","volume":"20","author":"Vazquez F.","year":"2000","unstructured":"F. Vazquez, S. Ramaswamy, N. Nakamura, W. R. Sellers, Phosphorylation of the PTEN tail regulates protein stability and function. J. Immunol. 20, 5010\u20135018 (2000).","journal-title":"J. Immunol."},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009134200"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.008"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10889-4"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-161"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.11.006"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601762"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-415380"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12741"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14032-1"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2771"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2017.01.004"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000584"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112378"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.07.010"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.22"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-08976-6"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abq3277"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2428"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-243071"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1024"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200001)30:1<155::AID-IMMU155>3.0.CO;2-X"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2011.155"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.07.034"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.201673"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01063"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.153411"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07595.x"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-280347"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903543106"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.21010"},{"key":"e_1_3_2_104_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky354"},{"key":"e_1_3_2_105_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202170126"},{"key":"e_1_3_2_106_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-801430-1.00005-6"}],"container-title":["Science Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.adj5948","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T13:58:25Z","timestamp":1705067905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.adj5948"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,12]]},"references-count":105,"journal-issue":{"issue":"91","published-print":{"date-parts":[[2024,1,12]]}},"alternative-id":["10.1126\/sciimmunol.adj5948"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.adj5948","relation":{},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,12]]},"assertion":[{"value":"2023-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadj5948"}}