{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T07:11:39Z","timestamp":1783408299324,"version":"3.54.6"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antibody production by the B cell compartment is a crucial part of the adaptive immune response. Dysregulated antibody production in the form of autoantibodies can cause autoimmune disease. To date, B\u2010cell depletion with anti\u2010CD20 antibodies is commonly applied in autoimmunity, but pre\u2010existing plasma cells are not eliminated in this way. Alternative ways of more selective inhibition of antibody production would add to the treatment of these autoimmune diseases. To explore novel therapeutic targets in signaling pathways essential for plasmablast formation and\/or immunoglobulin production, we performed a compound screen of almost 200 protein kinase inhibitors in a robust B\u2010cell differentiation culture system. This study yielded 35 small cell\u2010permeable compounds with a reproducible inhibitory effect on B\u2010cell activation and plasmablast formation, among which was the clinically applied mammalian target of rapamycin (mTOR) inhibitor rapamycin. Two additional compounds targeting the phosphoinositide 3\u2010kinase\u2010AKT\u2010mTOR pathway (BKM120 and WYE\u2010354) did not affect proliferation and plasmablast formation, but specifically reduced the immunoglobulin production. With this compound screen we successfully applied a method to investigate therapeutic targets for B\u2010cell differentiation and identified compounds in the phosphoinositide 3\u2010kinase\u2010AKT\u2010mTOR pathway that could specifically inhibit immunoglobulin production only. These drugs may well be explored to be of value in current B\u2010cell\u2010depleting treatment regimens in autoimmune disorders.<\/jats:p>","DOI":"10.1002\/eji.201948241","type":"journal-article","created":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T03:55:05Z","timestamp":1571284505000},"page":"73-85","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["High\u2010throughput compound screen reveals mTOR inhibitors as potential therapeutics to reduce (auto)antibody production by human plasma cells"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8233-8552","authenticated-orcid":false,"given":"Paul","family":"Tuijnenburg","sequence":"first","affiliation":[{"name":"Emma Children's Hospital Amsterdam UMC, University of Amsterdam Department of Pediatric Immunology Rheumatology and Infectious diseases  Amsterdam The Netherlands"},{"name":"Amsterdam UMC, University of Amsterdam Department of Experimental Immunology Amsterdam Infection &amp; Immunity Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan J.","family":"aan de Kerk","sequence":"additional","affiliation":[{"name":"Emma Children's Hospital Amsterdam UMC, University of Amsterdam Department of Pediatric Immunology Rheumatology and Infectious diseases  Amsterdam The Netherlands"},{"name":"Amsterdam UMC, University of Amsterdam Department of Experimental Immunology Amsterdam Infection &amp; Immunity Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machiel H.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Emma Children's Hospital Amsterdam UMC, University of Amsterdam Department of Pediatric Immunology Rheumatology and Infectious diseases  Amsterdam The Netherlands"},{"name":"Amsterdam UMC, University of Amsterdam Department of Experimental Immunology Amsterdam Infection &amp; Immunity Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Morris","sequence":"additional","affiliation":[{"name":"Division of Molecular Carcinogenesis and NKI Robotics and Screening Center Netherlands Cancer Institute (NKI\u2010AvL)  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cor","family":"Lieftink","sequence":"additional","affiliation":[{"name":"Division of Molecular Carcinogenesis and NKI Robotics and Screening Center Netherlands Cancer Institute (NKI\u2010AvL)  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick L.","family":"Beijersbergen","sequence":"additional","affiliation":[{"name":"Division of Molecular Carcinogenesis and NKI Robotics and Screening Center Netherlands Cancer Institute (NKI\u2010AvL)  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester M.M.","family":"van Leeuwen","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, University of Amsterdam Department of Experimental Immunology Amsterdam Infection &amp; Immunity Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taco W.","family":"Kuijpers","sequence":"additional","affiliation":[{"name":"Emma Children's Hospital Amsterdam UMC, University of Amsterdam Department of Pediatric Immunology Rheumatology and Infectious diseases  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3466"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI78084"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201807"},{"key":"e_1_2_8_5_1","first-page":"772","article-title":"Using large\u2010scale RNAi screens to identify novel drug targets for cancer","volume":"13","author":"Nijwening J. 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