{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:09:16Z","timestamp":1789463356117,"version":"build-2803163510"},"posted":{"date-parts":[[2026,7,21]]},"group-title":"Immunology","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["U19 AI110495"],"award-info":[{"award-number":["U19 AI110495"]}]},{"name":"NIH","award":["UM1 AI1144295"],"award-info":[{"award-number":["UM1 AI1144295"]}]},{"name":"NIH","award":["R01AI155447"],"award-info":[{"award-number":["R01AI155447"]}]},{"name":"NIH","award":["R01AI195539 P30AI060354"],"award-info":[{"award-number":["R01AI195539 P30AI060354"]}]},{"name":"NIH","award":["R21AI193280"],"award-info":[{"award-number":["R21AI193280"]}]},{"name":"NIH","award":["UM1 AI144462"],"award-info":[{"award-number":["UM1 AI144462"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Memory B cell recall responses are crucial for rapid protection from pathogens expressing previously encountered antigens. While germinal centers (GCs) contribute to durable B cell memory in many contexts, GC formation is attenuated or completely abrogated during some severe infections. Whether GC-independent responses generate functional memory B cells that may contribute to protective immunity remains unclear. Using mice lacking GCs, we identified a durable class-switched GC-independent memory B cell population that was generated dominantly through a T-cell-dependent response. Vaccine-induced non-GC memory B cells demonstrated greater diversity and provided humoral protection from matched and diverse vaccine-unmatched influenza viral challenges. These results identify a unique, durable, diverse, GC-independent memory B cell population that can mediate rapid protection from severe infections by mutable pathogens.<\/jats:p>","DOI":"10.64898\/2026.07.15.738751","type":"posted-content","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T17:40:15Z","timestamp":1784655615000},"source":"Crossref","is-referenced-by-count":0,"title":["Germinal center-independent memory B cells provide rapid protection from lethal influenza challenges"],"prefix":"10.64898","author":[{"given":"Elif","family":"\u00c7akan","sequence":"first","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faez Amokrane Nait","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anson","family":"Hui","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Essi C.","family":"Logan","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Ingram","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline A.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Smerczynski","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinmay Varma","family":"Gadiraju","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Barnes","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Mounier","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Walker","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD, USA"},{"name":"Institute for Medical Engineering and Science and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5631-9238","authenticated-orcid":false,"given":"Daniel","family":"Lingwood","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv","family":"Pillai","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091500550615000_2026.07.15.738751v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.016"},{"key":"2026091500550615000_2026.07.15.738751v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2014.02.010"},{"key":"2026091500550615000_2026.07.15.738751v1.3","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.23.3.284-a"},{"key":"2026091500550615000_2026.07.15.738751v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/J.IMMUNI.2019.07.001\/ATTACHMENT\/41BFE90E-9981-41C7-97D0-487629E99270\/MMC1.PDF"},{"key":"2026091500550615000_2026.07.15.738751v1.5","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20202489"},{"key":"2026091500550615000_2026.07.15.738751v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.025"},{"key":"2026091500550615000_2026.07.15.738751v1.7","first-page":"618","article-title":"Deficiency of Tfh Cells and Germinal Center in Deceased COVID-19 Patients. Curr","volume":"40","year":"2020","journal-title":"Med. Sci"},{"key":"2026091500550615000_2026.07.15.738751v1.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004976"},{"key":"2026091500550615000_2026.07.15.738751v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00814-z"},{"key":"2026091500550615000_2026.07.15.738751v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/jjmmuni.2025.08.007"},{"key":"2026091500550615000_2026.07.15.738751v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01721-9"},{"key":"2026091500550615000_2026.07.15.738751v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.08.015"},{"key":"2026091500550615000_2026.07.15.738751v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.11.006"},{"key":"2026091500550615000_2026.07.15.738751v1.14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072683"},{"key":"2026091500550615000_2026.07.15.738751v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43504-8"},{"key":"2026091500550615000_2026.07.15.738751v1.16","doi-asserted-by":"crossref","first-page":"eads8226","DOI":"10.1126\/sciimmunol.ads8226","article-title":"CD21 primes extrafollicular differentiation of autoreactive B cells in a TLR7-driven lupus model","volume":"10","year":"2025","journal-title":"Sci. Immunol"},{"key":"2026091500550615000_2026.07.15.738751v1.17","doi-asserted-by":"crossref","unstructured":"C. A. Perugino , H. Liu , J. Feldman , J. Marbourg , T. V. Guy , A. Hui , N. Ingram , J. Liebaert , N. Chaudhary , W. Tao , C. Jacob-Dolan , B. M. Hauser , Z. Mian , A. Nathan , Z. Zhao , C. Kaseke , R. Tano-Menka , M. A. Getz , F. Senjobe , C. Berrios , O. Ofoman , Z. Manickas-Hill , D. R. Wesemann , J. E. Lemieux , M. B. Goldberg , K. N\u00fcndel , A. Moormann , A. Marshak-Rothstein , R. C. Larocque , E. T. Ryan , J. A. Iafrate , D. Lingwood , G. Gaiha , R. Charles , A. B. Balazs , A. Pandit , V. Naranbhai , A. G. Schmidt , S. Pillai , Two distinct durable human class-switched memory B cell populations are induced by vaccination and infection. Cell Rep. 44, 115472 (2025).","DOI":"10.1016\/j.celrep.2025.115472"},{"key":"2026091500550615000_2026.07.15.738751v1.18","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl5652"},{"key":"2026091500550615000_2026.07.15.738751v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3563"},{"key":"2026091500550615000_2026.07.15.738751v1.20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300378"},{"key":"2026091500550615000_2026.07.15.738751v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.04.011"},{"key":"2026091500550615000_2026.07.15.738751v1.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1422269112"},{"key":"2026091500550615000_2026.07.15.738751v1.23","doi-asserted-by":"crossref","first-page":"5252","DOI":"10.4049\/jimmunol.150.12.5252","article-title":"Characterization of a novel cell-surface molecule expressed on subpopulations of activated T and B cells","volume":"150","year":"1993","journal-title":"J. Immunol"},{"key":"2026091500550615000_2026.07.15.738751v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.10.013"},{"key":"2026091500550615000_2026.07.15.738751v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3533"},{"key":"2026091500550615000_2026.07.15.738751v1.26","doi-asserted-by":"publisher","DOI":"10.1101\/2025.04.02.646697"},{"key":"2026091500550615000_2026.07.15.738751v1.27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701217"},{"key":"2026091500550615000_2026.07.15.738751v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.03.020"},{"key":"2026091500550615000_2026.07.15.738751v1.29","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20102065"},{"key":"2026091500550615000_2026.07.15.738751v1.30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1805268115"},{"key":"2026091500550615000_2026.07.15.738751v1.31","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01839-22"},{"key":"2026091500550615000_2026.07.15.738751v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.022"},{"key":"2026091500550615000_2026.07.15.738751v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3927"},{"key":"2026091500550615000_2026.07.15.738751v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.09.001"},{"key":"2026091500550615000_2026.07.15.738751v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.07.006"},{"key":"2026091500550615000_2026.07.15.738751v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.12.006"},{"key":"2026091500550615000_2026.07.15.738751v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.10.069"},{"key":"2026091500550615000_2026.07.15.738751v1.38","doi-asserted-by":"crossref","first-page":"eaef3415","DOI":"10.1126\/sciimmunol.aef3415","article-title":"Molecular and tissue regulation of memory B cells","volume":"11","year":"2026","journal-title":"Sci. Immunol"},{"key":"2026091500550615000_2026.07.15.738751v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01497-y"},{"key":"2026091500550615000_2026.07.15.738751v1.40","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/s41584-018-0113-6","article-title":"Double-negative B cells","volume":"14","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"2026091500550615000_2026.07.15.738751v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.06.024"},{"key":"2026091500550615000_2026.07.15.738751v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3443"},{"key":"2026091500550615000_2026.07.15.738751v1.43","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84428"},{"key":"2026091500550615000_2026.07.15.738751v1.44","doi-asserted-by":"crossref","unstructured":"M. Sangesland , D. Lingwood , Antibody Focusing to Conserved Sites of Vulnerability: The Immunological Pathways for \u201cUniversal\u201d Influenza Vaccines. Vaccines G , 125 (2021).","DOI":"10.3390\/vaccines9020125"},{"key":"2026091500550615000_2026.07.15.738751v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.048"},{"key":"2026091500550615000_2026.07.15.738751v1.46","doi-asserted-by":"crossref","unstructured":"A. L. Beukenhorst , K. L. Rice , J. Frallicciardi , M. H. Koldijk , C. M. Boudreau , J. Crawford , L. A. H. M. Cornelissen , K. A. S. da Costa , B. A. de Jong , S. Fischinger , B. Julg , J. M. Klap , C. M. Koch , Z. Magyarics , F. A. N. Mohamed , V. Okonkwo , L. Adams , C. M. McCarthy , L. Ronsard , N. Temperton , H. Vietsch , K. Wichapong , B. Ziere , D. Lingwood , J. Goudsmit , Intranasal administration of a panreactive influenza antibody reveals Fc-independent mode of protection. Sci. Rep. 15, 10309 (2025).","DOI":"10.1038\/s41598-025-94314-5"},{"key":"2026091500550615000_2026.07.15.738751v1.47","doi-asserted-by":"crossref","unstructured":"M. S. Miller , T. J. Gardner , F. Krammer , L. C. Aguado , D. Tortorella , C. F. Basler , P. Palese , Neutralizing Antibodies Against Previously Encountered Influenza Virus Strains Increase over Time: A Longitudinal Analysis. Sci. Transl. Med. 5 (2013).","DOI":"10.1126\/scitranslmed.3006637"},{"key":"2026091500550615000_2026.07.15.738751v1.48","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62105"},{"key":"2026091500550615000_2026.07.15.738751v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.022"},{"key":"2026091500550615000_2026.07.15.738751v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.009"},{"key":"2026091500550615000_2026.07.15.738751v1.51","doi-asserted-by":"crossref","unstructured":"V. C. Rosado , L. Adams , A. S. Yousif , M. Sangesland , L. Ronsard , V. Okonkwo , C. McCarthy , C. Alexander , D. Irvine , D. Lingwood , A modular protocol for virosome display of subunit vaccine antigens. STAR Protoc. 6, 103610 (2025).","DOI":"10.1016\/j.xpro.2025.103610"},{"key":"2026091500550615000_2026.07.15.738751v1.52","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03422-13"},{"key":"2026091500550615000_2026.07.15.738751v1.53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111497108"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.15.738751","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:09:54Z","timestamp":1789459794000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.07.15.738751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":53,"URL":"https:\/\/doi.org\/10.64898\/2026.07.15.738751","relation":{},"subject":[],"published":{"date-parts":[[2026,7,21]]},"subtype":"preprint"}}