{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:55:42Z","timestamp":1787972142515,"version":"build-2784847793"},"reference-count":82,"publisher":"Life Science Alliance, LLC","issue":"9","license":[{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Top Sector Life Sciences and Health to Samenwerkende Gezondheidsfondsen","award":["LSHM18055-SGF"],"award-info":[{"award-number":["LSHM18055-SGF"]}]}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:p>B cell\u2013targeted therapies, such as CD20-targeting mAbs, deplete B cells but do not target the autoantibody-producing plasma cells (PCs). PC-targeting therapies such as daratumumab (anti-CD38) form an attractive approach to treat PC-mediated diseases. CD38 possesses enzymatic and receptor capabilities, which may impact a range of cellular processes including proliferation and differentiation. However, very little is known whether and how CD38 targeting affects B-cell differentiation, in particular for humans beyond cancer settings. Using in-depth in vitro B-cell differentiation assays and signaling pathway analysis, we show that CD38 targeting with daratumumab demonstrated a significant decrease in proliferation, differentiation, and IgG production upon T cell\u2013dependent B-cell stimulation. We found no effect on T-cell activation or proliferation. Furthermore, we demonstrate that daratumumab attenuated the activation of NF-\u03baB in B cells and the transcription of NF-\u03baB\u2013targeted genes. When culturing sorted B-cell subsets with daratumumab, the switched memory B-cell subset was primarily affected. Overall, these in vitro data elucidate novel non-depleting mechanisms by which daratumumab can disturb humoral immune responses. Affecting memory B cells, daratumumab may be used as a therapeutic approach in B cell\u2013mediated diseases other than the currently targeted malignancies.<\/jats:p>","DOI":"10.26508\/lsa.202302214","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T13:15:19Z","timestamp":1688735719000},"page":"e202302214","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["B-cell targeting with anti-CD38 daratumumab: implications for differentiation and memory responses"],"prefix":"10.26508","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5837-6068","authenticated-orcid":true,"given":"Dorit","family":"Verhoeven","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05grdyy37","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC","place":[", University of Amsterdam, Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children\u2019s Hospital, Amsterdam, The Netherlands"]},{"id":[{"id":"https:\/\/ror.org\/05grdyy37","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC","place":[", University of Amsterdam, Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Grinwis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05grdyy37","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC","place":[", University of Amsterdam, Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper","family":"Marsman","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Department of Immunopathology, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machiel H","family":"Jansen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05grdyy37","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC","place":[", University of Amsterdam, Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"T2B Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester MM","family":"Van Leeuwen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05grdyy37","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC","place":[", University of Amsterdam, Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taco W","family":"Kuijpers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05grdyy37","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC","place":[", University of Amsterdam, Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children\u2019s Hospital, Amsterdam, The Netherlands"]},{"id":[{"id":"https:\/\/ror.org\/05grdyy37","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC","place":[", University of Amsterdam, Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"12380","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"2023082513251176000_6.9.e202302214.1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3795"},{"key":"2023082513251176000_6.9.e202302214.2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12754"},{"key":"2023082513251176000_6.9.e202302214.3","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.7867"},{"key":"2023082513251176000_6.9.e202302214.4","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747168"},{"key":"2023082513251176000_6.9.e202302214.5","doi-asserted-by":"publisher","DOI":"10.1038\/ni1454"},{"key":"2023082513251176000_6.9.e202302214.6","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0042"},{"key":"2023082513251176000_6.9.e202302214.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-020-00359-2"},{"key":"2023082513251176000_6.9.e202302214.8","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.194282"},{"key":"2023082513251176000_6.9.e202302214.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31240-1"},{"key":"2023082513251176000_6.9.e202302214.10","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121629"},{"key":"2023082513251176000_6.9.e202302214.11","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01090-6"},{"key":"2023082513251176000_6.9.e202302214.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.06.014"},{"key":"2023082513251176000_6.9.e202302214.13","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021013714"},{"key":"2023082513251176000_6.9.e202302214.14","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15433"},{"key":"2023082513251176000_6.9.e202302214.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtauto.2019.100022"},{"key":"2023082513251176000_6.9.e202302214.16","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010228"},{"key":"2023082513251176000_6.9.e202302214.17","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14174169"},{"key":"2023082513251176000_6.9.e202302214.18","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2002700"},{"key":"2023082513251176000_6.9.e202302214.19","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.12.14.1507"},{"key":"2023082513251176000_6.9.e202302214.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2021.102514"},{"key":"2023082513251176000_6.9.e202302214.21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.51.30327"},{"key":"2023082513251176000_6.9.e202302214.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.05.006"},{"key":"2023082513251176000_6.9.e202302214.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.04.003"},{"key":"2023082513251176000_6.9.e202302214.24","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8736949"},{"key":"2023082513251176000_6.9.e202302214.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.08.066"},{"key":"2023082513251176000_6.9.e202302214.26","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.160.1.395"},{"key":"2023082513251176000_6.9.e202302214.27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.4.1455"},{"key":"2023082513251176000_6.9.e202302214.28","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20220201"},{"key":"2023082513251176000_6.9.e202302214.29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201807"},{"key":"2023082513251176000_6.9.e202302214.30","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201948241"},{"key":"2023082513251176000_6.9.e202302214.31","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0477-1"},{"key":"2023082513251176000_6.9.e202302214.32","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v128.22.5630.5630"},{"key":"2023082513251176000_6.9.e202302214.33","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.169235"},{"key":"2023082513251176000_6.9.e202302214.34","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.21961"},{"key":"2023082513251176000_6.9.e202302214.35","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.36"},{"key":"2023082513251176000_6.9.e202302214.36","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.11.7276"},{"key":"2023082513251176000_6.9.e202302214.37","doi-asserted-by":"publisher","DOI":"10.1158\/2767-9764.crc-22-0083"},{"key":"2023082513251176000_6.9.e202302214.38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003032"},{"key":"2023082513251176000_6.9.e202302214.39","doi-asserted-by":"publisher","DOI":"10.1007\/82_2015_479"},{"key":"2023082513251176000_6.9.e202302214.40","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1368"},{"key":"2023082513251176000_6.9.e202302214.41","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf660"},{"key":"2023082513251176000_6.9.e202302214.42","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401838"},{"key":"2023082513251176000_6.9.e202302214.43","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.6336"},{"key":"2023082513251176000_6.9.e202302214.44","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122633"},{"key":"2023082513251176000_6.9.e202302214.45","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00035.2007"},{"key":"2023082513251176000_6.9.e202302214.46","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-12-687749"},{"key":"2023082513251176000_6.9.e202302214.47","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2022-002742"},{"key":"2023082513251176000_6.9.e202302214.48","doi-asserted-by":"publisher","DOI":"10.21608\/EJHM.2021.184227"},{"key":"2023082513251176000_6.9.e202302214.49","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.577"},{"key":"2023082513251176000_6.9.e202302214.50","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-123169"},{"key":"2023082513251176000_6.9.e202302214.51","doi-asserted-by":"publisher","DOI":"10.1177\/10600280211058754"},{"key":"2023082513251176000_6.9.e202302214.52","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-127247"},{"key":"2023082513251176000_6.9.e202302214.53","doi-asserted-by":"publisher","DOI":"10.1177\/20406207211035272"},{"key":"2023082513251176000_6.9.e202302214.54","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.279232"},{"key":"2023082513251176000_6.9.e202302214.55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0211927"},{"key":"2023082513251176000_6.9.e202302214.56","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01183-2"},{"key":"2023082513251176000_6.9.e202302214.57","doi-asserted-by":"publisher","DOI":"10.3390\/cells9071716"},{"key":"2023082513251176000_6.9.e202302214.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2019.11.005"},{"key":"2023082513251176000_6.9.e202302214.59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01187"},{"key":"2023082513251176000_6.9.e202302214.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.10.006"},{"key":"2023082513251176000_6.9.e202302214.61","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17329"},{"key":"2023082513251176000_6.9.e202302214.62","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121522"},{"key":"2023082513251176000_6.9.e202302214.63","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4693"},{"key":"2023082513251176000_6.9.e202302214.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103616"},{"key":"2023082513251176000_6.9.e202302214.65","doi-asserted-by":"publisher","DOI":"10.3390\/genes12111698"},{"key":"2023082513251176000_6.9.e202302214.66","doi-asserted-by":"publisher","DOI":"10.2174\/138945012799201711"},{"key":"2023082513251176000_6.9.e202302214.67","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02921.x"},{"key":"2023082513251176000_6.9.e202302214.68","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay2793"},{"key":"2023082513251176000_6.9.e202302214.69","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.231860"},{"key":"2023082513251176000_6.9.e202302214.70","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1086"},{"key":"2023082513251176000_6.9.e202302214.71","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.667515"},{"key":"2023082513251176000_6.9.e202302214.72","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09585-6"},{"key":"2023082513251176000_6.9.e202302214.73","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.602102"},{"key":"2023082513251176000_6.9.e202302214.74","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25932"},{"key":"2023082513251176000_6.9.e202302214.75","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.649441"},{"key":"2023082513251176000_6.9.e202302214.76","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2028631"},{"key":"2023082513251176000_6.9.e202302214.77","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26517"},{"key":"2023082513251176000_6.9.e202302214.78","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018020883"},{"key":"2023082513251176000_6.9.e202302214.79","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019001215"},{"key":"2023082513251176000_6.9.e202302214.80","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1807438"},{"key":"2023082513251176000_6.9.e202302214.81","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020101541"},{"key":"2023082513251176000_6.9.e202302214.82","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2023325"}],"container-title":["Life Science Alliance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.26508\/lsa.202302214","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T09:07:47Z","timestamp":1704877667000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.life-science-alliance.org\/lookup\/doi\/10.26508\/lsa.202302214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,7]]},"references-count":82,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,7,7]]},"published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.26508\/lsa.202302214"],"URL":"https:\/\/doi.org\/10.26508\/lsa.202302214","relation":{},"ISSN":["2575-1077"],"issn-type":[{"value":"2575-1077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,7]]}}}