{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:55:44Z","timestamp":1793156144936,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Plasma cells provide protective antibodies following an infection or vaccination. A network of intrinsic and extrinsic factors fine-tunes the generation of a heterogenous plasma cell pool with varying metabolic requirements, transcriptional profiles and lifespans. Among these, the B cell maturation antigen (BCMA) has been implicated in the APRIL-mediated survival of long-lived plasma cells. To characterize the terminal maturation of plasma cells, we constructed a BCMA reporter mouse (BCMA:Tom) that exclusively labeled antibody-secreting cells and revealed that BCMA:Tom expression varied by IgH isotype and increased with plasma cell maturity. The BCMA reporter, used alongside the Blimp1-GFP reporter, also allowed detailed tracking of plasma cell development and highlighted the importance of the\n                    <jats:italic>in vivo<\/jats:italic>\n                    microenvironment to complete plasma cell maturation. Therefore, the BCMA:Tom reporter mouse provides a valuable tool for tracking plasma cell development and maturation with flow cytometry or advanced imaging techniques, enabling a deeper understanding of the mechanisms regulating plasma cell heterogeneity and longevity.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1539773","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T01:11:36Z","timestamp":1741655496000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Decoding plasma cell maturation dynamics with BCMA"],"prefix":"10.3389","volume":"16","author":[{"given":"Sebastian R.","family":"Schulz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon R.","family":"Menzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Wittner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Ulbricht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina T.","family":"Grofe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Mann-N\u00fcttel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Scheu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Kueh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"J\u00e4ck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco J.","family":"Herold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja E.","family":"Hauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Pracht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Schuh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Martin","family":"J\u00e4ck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161590","article-title":"Antibody-secreting plasma cells persist for decades in human intestine","volume":"214","author":"Landsverk","year":"2017","journal-title":"J Exp Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1016\/j.immuni.2023.04.015","article-title":"Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan","volume":"56","author":"Robinson","year":"2023","journal-title":"Immunity"},{"key":"B3","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/mi.2015.38","article-title":"Long-lived plasma cells are generated in mucosal immune responses and contribute to the bone marrow plasma cell pool in mice","volume":"9","author":"Lemke","year":"2016","journal-title":"Mucosal Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/s41590-023-01712-w","article-title":"Unraveling the diversity and functions of tissue-resident plasma cells","volume":"25","author":"Tellier","year":"2024","journal-title":"Nat Immunol"},{"key":"B5","first-page":"57","article-title":"Unraveling the mysteries of plasma cells","volume-title":"Advances in immunology","author":"Schuh","year":"2020"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12346","article-title":"Do plasma cells contribute to the determination of their lifespan","volume":"98","author":"Tarlinton","year":"2020","journal-title":"Immunol Cell Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031330","article-title":"BCMA is essential for the survival of long-lived bone marrow plasma cells","volume":"199","author":"O\u2019Connor","year":"2004","journal-title":"J Exp Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1038\/s41375-020-0734-z","article-title":"B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches | Leukemia","volume":"34","author":"Shah","year":"2020","journal-title":"Leukemia"},{"key":"B9","doi-asserted-by":"publisher","first-page":"7333","DOI":"10.1038\/ncomms8333","article-title":"\u03b3-secretase directly sheds the survival receptor BCMA from plasma cells","volume":"6","author":"Laurent","year":"2015","journal-title":"Nat Commun"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040973","article-title":"Plasma cell ontogeny defined by quantitative changes in blimp-1 expression","volume":"200","author":"Kallies","year":"2004","journal-title":"J Exp Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41385-022-00503-0","article-title":"Kr\u00fcppel-like factor 2 controls IgA plasma cell compartmentalization and IgA responses","volume":"15","author":"Wittner","year":"2022","journal-title":"Mucosal Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/ncomms1475","article-title":"In-vitro derived germinal centre B cells differentially generate memory B or plasma cells","volume":"2","author":"Nojima","year":"2011","journal-title":"vivo. Nat Commun"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/5.6.647","article-title":"Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus","volume":"5","author":"Chen","year":"1993","journal-title":"Int Immunol"},{"key":"B14","first-page":"EP3572427A1","volume-title":"BCMA-targeting antibody and use thereof","author":"Wang","year":"2019"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2007.09.017","article-title":"Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning","volume":"329","author":"Tiller","year":"2008","journal-title":"J Immunol Methods"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202149374","article-title":"A pair of noncompeting neutralizing human monoclonal antibodies protecting from disease in a SARS-CoV-2 infection model","volume":"52","author":"Peter","year":"2022","journal-title":"Eur J Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR+x202F;: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-02014-7","article-title":"Extending support for mouse data in the Molecular Signatures Database (MSigDB)","volume":"20","author":"Castanza","year":"2023","journal-title":"Nat Methods"},{"key":"B21","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3364","article-title":"MiXCR: software for comprehensive adaptive immunity profiling","volume":"12","author":"Bolotin","year":"2015","journal-title":"Nat Methods"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900285","article-title":"IgM, igG, and igA influenza-specific plasma cells express divergent transcriptomes","volume":"203","author":"Price","year":"2019","journal-title":"JI"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.1038\/s41467-024-45827-6","article-title":"MarShie: a clearing protocol for 3D analysis of single cells throughout the bone marrow at subcellular resolution","volume":"15","author":"Mertens","year":"2024","journal-title":"Nat Commun"},{"key":"B25","doi-asserted-by":"publisher","first-page":"7101","DOI":"10.1038\/s41598-017-07165-0","article-title":"Synergistic Strategy for Multicolor Two-photon Microscopy: Application to the Analysis of Germinal Center Reactions In Vivo","volume":"7","author":"Rakhymzhan","year":"2017","journal-title":"Sci Rep"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747019","article-title":"A new staining protocol for detection of murine antibody-secreting plasma cell subsets by flow cytometry","volume":"47","author":"Pracht","year":"2017","journal-title":"Eur J Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/art.38950","article-title":"BAFF regulates follicular helper T cells and affects their accumulation and interferon-\u03b3 Production in autoimmunity","volume":"67","author":"Coquery","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3478","article-title":"Open-source ImmGen: mononuclear phagocytes","volume":"17","year":"2016","journal-title":"Nat Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.598500","article-title":"Genetic timestamping of plasma cells in vivo reveals tissue-specific homeostatic population turnover","volume":"9","author":"Xu","year":"2020","journal-title":"eLife"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1037","article-title":"Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein","volume":"22","author":"Shaner","year":"2004","journal-title":"Nat Biotechnol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2467","article-title":"A robust and high-throughput Cre reporting and characterization system for the whole mouse brain","volume":"13","author":"Madisen","year":"2010","journal-title":"Nat Neurosci"},{"key":"B32","volume-title":"Transcriptomic analysis of mouse preimplantation embryo development and nutrient provision","author":"Chi","year":"2020"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112352","article-title":"BAFF and APRIL counterregulate susceptibility to inflammation-induced preterm birth","volume":"42","author":"Doll","year":"2023","journal-title":"Cell Rep"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nature03813","article-title":"Blimp1 is a critical determinant of the germ cell lineage in mice","volume":"436","author":"Ohinata","year":"2005","journal-title":"Nature"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.791095","article-title":"IgA plasma cells are long-lived residents of gut and bone marrow that express isotype- and tissue-specific gene expression patterns","volume":"12","author":"Wilmore","year":"2021","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00267-X","article-title":"Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells","volume":"19","author":"Shapiro-Shelef","year":"2003","journal-title":"Immunity"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.61","article-title":"IL-6 supports the generation of human long-lived plasma cells in combination with either APRIL or stromal cell-soluble factors","volume":"28","author":"Jourdan","year":"2014","journal-title":"Leukemia"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-010-0028-z","article-title":"B-lymphocyte-induced maturation protein1 up-regulates the expression of B-cell maturation antigen in mouse plasma cells","volume":"37","author":"Deng","year":"2010","journal-title":"Mol Biol Rep"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2634","DOI":"10.1016\/j.celrep.2019.10.097","article-title":"IRF4 activity is required in established plasma cells to regulate gene transcription and mitochondrial homeostasis","volume":"29","author":"Low","year":"2019","journal-title":"Cell Rep"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3154","article-title":"Transcriptional profiling of mouse B cell terminal differentiation defines a signature for antibody-secreting plasma cells","volume":"16","author":"Shi","year":"2015","journal-title":"Nat Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"RP89712","DOI":"10.7554\/eLife.89712.3","article-title":"Fine-tuning spatial-temporal dynamics and surface receptor expression support plasma cell-intrinsic longevity","volume":"12","author":"Jing","year":"2024","journal-title":"eLife"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809736106","article-title":"CD93 is required for maintenance of antibody secretion and persistence of plasma cells in the bone marrow niche","volume":"106","author":"Chevrier","year":"2009","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00788","article-title":"In the right place, at the right time: spatiotemporal conditions determining plasma cell survival and function","volume":"10","author":"Lindquist","year":"2019","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100623","article-title":"APRIL drives a coordinated but diverse response as a foundation for plasma cell longevity","volume":"209","author":"Stephenson","year":"2022","journal-title":"J Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100004","article-title":"A system for in vitro generation of mature murine plasma cells uncovers differential blimp-1\/prdm1 promoter usage","volume":"208","author":"Robinson","year":"2022","journal-title":"J Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"6110","DOI":"10.1038\/s41467-022-33787-8","article-title":"Ex vivo engineered human plasma cells exhibit robust protein secretion and long-term engraftment","volume":"13","author":"Cheng","year":"2022","journal-title":"vivo. Nat Commun"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1539773\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T01:11:41Z","timestamp":1741655501000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1539773\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,11]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2025.1539773"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1539773","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,11]]},"article-number":"1539773"}}