{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:12:49Z","timestamp":1789755169922,"version":"4.0.1"},"reference-count":75,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"123","funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP223fa627002"],"award-info":[{"award-number":["JP223fa627002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["J243100002"],"award-info":[{"award-number":["J243100002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP223fa627002"],"award-info":[{"award-number":["JP223fa627002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["J243100002"],"award-info":[{"award-number":["J243100002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shionogi Next Generation Researchers Support for Fundamental or Drug Discovery Research under Number","award":["J253100004"],"award-info":[{"award-number":["J253100004"]}]},{"name":"IFReC Kishimoto Foundation Fellowship"},{"name":"IFReC Advanced Post-doc Program"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2026,9,18]]},"abstract":"<jats:p>\n                    During antibody responses, germinal centers (GCs) act as a key site for somatic hypermutation (SHM) and affinity maturation of B cells. However, their lymphoid tissue localization has made experimental manipulation of human germinal center B (GCB) cells difficult. Here, we describe a simple in vitro method, modeling T cell\u2013derived signaling, that converts human naive B cells into BCL6\n                    <jats:sup>+<\/jats:sup>\n                    induced GCB-like (iGCB) cells. Through side-by-side proteomic and transcriptional single-cell analysis of iGCB and human tonsil GCB cells, we show that iGCB cells recapitulate the surface marker, transcription factor, DNA repair, and glycosylation signatures that define human GCB cells and display ongoing activation-induced cytidine deaminase (AID)\u2013dependent SHM. iGCB cells can be generated from naive B cells and from unswitched memory\/circulating marginal zone cells but not class-switched memory B cells. Using this system, we define signals critical for human GCB formation and identify interventions that block their induction, providing a simple and manipulable model of human GCB cell biology.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.aeg5223","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:58:23Z","timestamp":1789754303000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["In vitro induction of human germinal center B cells"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0095-6718","authenticated-orcid":true,"given":"David G.","family":"Priest","sequence":"first","affiliation":[{"name":"Human Single Cell Immunology Team, Division of Microbiology and Immunology, Center for Infectious Disease Education and Research (CiDER), University of Osaka, Suita, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melike Fusun","family":"Demir","sequence":"additional","affiliation":[{"name":"Laboratory of Human Single Cell Immunology, World Premier International Research Center Initiative Immunology Frontier Research Center (WPI-IFReC), University of Osaka, Suita, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0457-3386","authenticated-orcid":true,"given":"Wataru","family":"Ise","sequence":"additional","affiliation":[{"name":"Regulation of Host Defense Team, Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, University of Osaka, Suita, Osaka, Japan."},{"name":"Center for Advanced Modalities and DDS (CAMaD), University of Osaka, Suita, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3462-1003","authenticated-orcid":true,"given":"James B.","family":"Wing","sequence":"additional","affiliation":[{"name":"Human Single Cell Immunology Team, Division of Microbiology and Immunology, Center for Infectious Disease Education and Research (CiDER), University of Osaka, Suita, Osaka, Japan."},{"name":"Laboratory of Human Single Cell Immunology, World Premier International Research Center Initiative Immunology Frontier Research Center (WPI-IFReC), University of Osaka, Suita, Osaka, Japan."},{"name":"Center for Advanced Modalities and DDS (CAMaD), University of Osaka, Suita, Osaka, Japan."},{"name":"Bioinformatics Center (OUBIC), Research Institute for Microbial Diseases, University of Osaka, Suita, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-120419-022408"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00446-2"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.825813"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2024.102428"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.036"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.02.018"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091738"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091777"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.1.157"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1257861"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.04.011"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abe6291"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200483"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.10.032"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1475"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12283"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.115190"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03738-2"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-02064-9"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07748-8"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44321-025-00193-8"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102684"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01145-0"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.06.019"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-3950-4_1"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-024-02037-1"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105741"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.3.1767"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.7867"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051183"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.815449"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.83578"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5312.589"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4437"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1830-0"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20240668"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01142-2"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08728-2"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08687-8"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.06.013"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.891316"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20132203"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500753"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06089-1"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20202001"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.11.006"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-041015-055605"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.3.439"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1837"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2025.111242"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.01.009"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.025"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.024"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.4110\/in.2024.24.e8"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200922"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.08.028"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3554"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.165.6.1459"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.744573"},{"key":"e_1_3_2_61_2","doi-asserted-by":"crossref","unstructured":"S. G. Tangye J. L. Casanova C. S. Ma \u201cHuman immunodeficiencies caused by inborn errors of B-cell development or function \u201d in Molecular Biology of B Cells (Academic Press 2024).","DOI":"10.1016\/B978-0-323-95895-0.00013-1"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20221105"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1308378"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091087"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1342"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7095-7_11"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03382-x"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060139"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200010)30:10<3039::AID-IMMU3039>3.0.CO;2-H"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50997-4"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.11622.1"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55746-1"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv359"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00358"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009885"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2300851"}],"container-title":["Science Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.aeg5223","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:58:26Z","timestamp":1789754306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.aeg5223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":75,"journal-issue":{"issue":"123","published-print":{"date-parts":[[2026,9,18]]}},"alternative-id":["10.1126\/sciimmunol.aeg5223"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.aeg5223","relation":{},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]},"assertion":[{"value":"2026-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaeg5223"}}