{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:20:41Z","timestamp":1791908441027,"version":"4.3.4"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The thymus contains various antigen-presenting cells, including B cells, which remain activated even under steady-state conditions, suggesting ongoing local stimulation. In this study, we identify class-switched memory B cells in the thymus. Some of these cells switch their immunoglobulin to IgG2b and IgA, and express typical memory markers CD73 and PD-L2. Memory B cell differentiation in the thymus begins in neonatal mice, preceding the appearance of class-switched B cells in other peripheral lymphoid organs. Notably, exposure to environmental antigens does not influence their differentiation. Additionally, cognate interaction with CD4\n                    <jats:sup>+<\/jats:sup>\n                    positive thymocytes is crucial for the development of memory B cells in the thymus. Our findings demonstrate that the thymus supports the local differentiation of memory B cells through a steady-state process, independent of foreign antigen stimulation and driven by interactions with developing T cells.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1567788","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T01:52:01Z","timestamp":1743126721000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Early-life homeostatic differentiation of thymus-resident B cells into memory B cells"],"prefix":"10.3389","volume":"16","author":[{"given":"Justine","family":"Casta\u00f1eda","sequence":"first","affiliation":[{"name":"Escuela de Postgrado, Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian","family":"Poblete","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda, Facultad de Ciencias, Universidad de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana V.","family":"Rosemblatt","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Sede Los Leones","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Sauma","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda, Facultad de Ciencias, Universidad de Chile","place":["Santiago, Chile"]},{"name":"Centro Ciencia & Vida","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Rosemblatt","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda, Facultad de Ciencias, Universidad de Chile","place":["Santiago, Chile"]},{"name":"Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Sede Los Leones","place":["Santiago, Chile"]},{"name":"Centro Ciencia & Vida","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Rosa","family":"Bono","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda, Facultad de Ciencias, Universidad de Chile","place":["Santiago, Chile"]},{"name":"Centro Ciencia & Vida","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Nu\u00f1ez","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Sede Los Leones","place":["Santiago, Chile"]},{"name":"Centro Ciencia & Vida","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.168.2.811","article-title":"Unusual phenotype of B cells in the thymus of normal mice","volume":"168","author":"Miyama-Inaba","year":"1988","journal-title":"J Exp Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(87)92622-5","article-title":"The human thymus contains a novel population of B lymphocytes","volume":"2","author":"Isaacson","year":"1987","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.10.5221","article-title":"B lymphopoiesis in the thymus","volume":"164","author":"Akashi","year":"2000","journal-title":"J Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1093\/intimm\/14.1.87","article-title":"The ontogeny of B cells in the thymus of normal, CD3 epsilon knockout (KO), RAG-2 KO and IL-7 transgenic mice","volume":"14","author":"Ceredig","year":"2002","journal-title":"Int Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.151.1.100","article-title":"Characterization of a novel CD2+ human thymic B cell subset","volume":"151","author":"Punnonen","year":"1993","journal-title":"J Immunol"},{"key":"B6","first-page":"596","article-title":"Properties of human thymic B cells","volume":"75","author":"Spencer","year":"1992","journal-title":"Immunology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aah4447","article-title":"The human thymus perivascular space is a functional niche for viral-specific plasma cells","volume":"1","author":"Nu\u00f1ez","year":"2016","journal-title":"Sci Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.01.015","article-title":"Age-associated decline in thymic B cell expression of aire and aire-dependent self-antigens","volume":"22","author":"Cepeda","year":"2018","journal-title":"Cell Rep"},{"key":"B9","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.jaut.2015.05.008","article-title":"Thymic B cells promote thymus-derived regulatory T cell development and proliferation","volume":"61","author":"Lu","year":"2015","journal-title":"J Autoimmun"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302519","article-title":"A role for intrathymic B cells in the generation of natural regulatory T cells","volume":"193","author":"Walters","year":"2014","journal-title":"J Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.05.013","article-title":"Thymic B cells are licensed to present self antigens for central T cell tolerance induction","volume":"42","author":"Yamano","year":"2015","journal-title":"Immunity"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.08.007","article-title":"AIRE in the thymus and beyond","volume":"21","author":"Gardner","year":"2009","journal-title":"Curr Opin Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1313001110","article-title":"Autoreactive thymic B cells are efficient antigen-presenting cells of cognate self-antigens for T cell negative selection","volume":"110","author":"Perera","year":"2013","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199905)29:05<1598::AID-IMMU1598>3.0.CO;2-O","article-title":"Functional and phenotypic analysis of thymic B cells: role in the induction of T cell negative selection","volume":"29","author":"Ferrero","year":"1999","journal-title":"Eur J Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1146\/annurev.immunol.23.021704.115732","article-title":"Antigen-specific memory B cell development","volume":"23","author":"McHeyzer-Williams","year":"2005","journal-title":"Annu Rev Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nri3802","article-title":"Memory B cells","volume":"15","author":"Kurosaki","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/imr.13016","article-title":"Memory B cells and plasma cells: The differentiative continuum of humoral immunity","volume":"303","author":"Cancro","year":"2021","journal-title":"Immunol Rev"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00938.x","article-title":"Memory B and memory plasma cells","volume":"237","author":"Yoshida","year":"2010","journal-title":"Immunol Rev"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002163","article-title":"Cutting edge: Hierarchy of maturity of murine memory B cell subsets","volume":"185","author":"Tomayko","year":"2010","journal-title":"J Immunol"},{"key":"B20","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/s41467-017-00723-0","article-title":"IgG1 memory B cells keep the memory of IgE responses","volume":"8","author":"He","year":"2017","journal-title":"Nat Commun"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.44245","article-title":"The quantity of CD40 signaling determines the differentiation of B cells into functionally distinct memory cell subsets","volume":"8","author":"Koike","year":"2019","journal-title":"Elife"},{"key":"B22","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41590-018-0260-6","article-title":"The establishment of resident memory B cells in the lung requires local antigen encounter","volume":"20","author":"Allie","year":"2019","journal-title":"Nat Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2914","article-title":"CD80 and PD-L2 define functionally distinct memory B cell subsets that are independent of antibody isotype","volume":"15","author":"Zuccarino-Catania","year":"2014","journal-title":"Nat Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115369109","article-title":"Memory B cells in the lung participate in protective humoral immune responses to pulmonary influenza virus reinfection","volume":"109","author":"Onodera","year":"2012","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01787","article-title":"Remembrance of things past: long-term B cell memory after infection and vaccination","volume":"10","author":"Palm","year":"2019","journal-title":"Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343716","article-title":"Generation of memory B cells inside and outside germinal centers","volume":"44","author":"Takemori","year":"2014","journal-title":"Eur J Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI141810","article-title":"Lung-resident memory B cells protect against bacterial pneumonia","volume":"131","author":"Barker","year":"2021","journal-title":"J Clin Invest"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abj5129","article-title":"Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA","volume":"6","author":"Oh","year":"2021","journal-title":"Sci Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf5314","article-title":"Lung-resident memory B cells established after pulmonary influenza infection display distinct transcriptional and phenotypic profiles","volume":"7","author":"Tan","year":"2022","journal-title":"Sci Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"7081","DOI":"10.1038\/s41467-023-42625-4","article-title":"Tissue-resident B cells orchestrate macrophage polarisation and function","volume":"14","author":"Suchanek","year":"2023","journal-title":"Nat Commun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4103\/0976-500X.119726","article-title":"How to calculate sample size in animal studies","volume":"4","author":"Charan","year":"2013","journal-title":"J Pharmacol Pharmacother"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00696","article-title":"Thymic B cells promote germinal center-like structures and the expansion of follicular helper T cells in lupus-prone mice","volume":"11","author":"Hidalgo","year":"2020","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2022.993658","article-title":"An optimized mouse parabiosis protocol for investigation of aging and rejuvenative mechanisms","volume":"3","author":"Rodriguez","year":"2022","journal-title":"Front Aging"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13839","article-title":"The microbiota maintain homeostasis of liver-resident \u03b3\u03b4T-17 cells in a lipid antigen\/CD1d-dependent manner","volume":"7","author":"Li","year":"2017","journal-title":"Nat Commun"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e27662","DOI":"10.1371\/journal.pone.0027662","article-title":"The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice","volume":"6","author":"Lamous\u00e9-Smith","year":"2011","journal-title":"PloS One"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3542","article-title":"The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice","volume":"20","author":"Deshmukh","year":"2014","journal-title":"Nat Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502322","article-title":"Maternal antibiotic treatment impacts development of the neonatal intestinal microbiome and antiviral immunity","volume":"196","author":"Gonzalez-Perez","year":"2016","journal-title":"J Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e52591","DOI":"10.1371\/journal.pone.0052591","article-title":"Antigen recognition by autoreactive CD4+ thymocytes drives homeostasis of the thymic medulla","volume":"7","author":"Irla","year":"2012","journal-title":"PloS One"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf4822","article-title":"IgA production requires B cell interaction with subepithelial dendritic cells in Peyer\u2019s patches","volume":"352","author":"Reboldi","year":"2016","journal-title":"Science"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12400","article-title":"Peyer\u2019s patches: organizing B-cell responses at the intestinal frontier","volume":"271","author":"Reboldi","year":"2016","journal-title":"Immunol Rev"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01078-x","article-title":"Surface phenotypes of naive and memory B cells in mouse and human tissues","volume":"23","author":"Weisel","year":"2022","journal-title":"Nat Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2013.07.006","article-title":"A comparative review of aging and B cell function in mice and humans","volume":"25","author":"Scholz","year":"2013","journal-title":"Curr Opin Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.011","article-title":"Self-antigen-driven thymic B cell class switching promotes T cell central tolerance","volume":"17","author":"Perera","year":"2016","journal-title":"Cell Rep"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1038\/s41467-022-29032-x","article-title":"Homeostatic serum IgE is secreted by plasma cells in the thymus and enhances mast cell survival","volume":"13","author":"Kwon","year":"2022","journal-title":"Nat Commun"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.07.015","article-title":"The unique biology of germinal center B cells","volume":"54","author":"Young","year":"2021","journal-title":"Immunity"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.07.001","article-title":"Class-switch recombination occurs infrequently in germinal centers","volume":"51","author":"Roco","year":"2019","journal-title":"Immunity"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1996.499573.x","article-title":"Thymic B cells of pig fetuses and germ-free pigs spontaneously produce IgM, IgG and IgA: detection by ELISPOT method","volume":"87","author":"Cukrowska","year":"1996","journal-title":"Immunology"}],"updated-by":[{"DOI":"10.3389\/fimmu.2026.1783042","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000}}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1567788\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T14:30:02Z","timestamp":1769437802000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1567788\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,28]]},"references-count":47,"alternative-id":["10.3389\/fimmu.2025.1567788"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1567788","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,28]]},"article-number":"1567788"}}