{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:09:47Z","timestamp":1791850187793,"version":"4.3.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["R01 AI153425"],"award-info":[{"award-number":["R01 AI153425"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["U19 AI089674"],"award-info":[{"award-number":["U19 AI089674"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["T32 AI138944"],"award-info":[{"award-number":["T32 AI138944"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["T32 AI138944"],"award-info":[{"award-number":["T32 AI138944"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TL1 TR002647"],"award-info":[{"award-number":["TL1 TR002647"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Chronic and frequently recurring infectious diseases, such as malaria, are associated with expanded populations of atypical memory B cells (MBCs). These cells are different from classical MBCs by the lack of surface markers CD21 and CD27 and increased expression of inhibitory receptors, such as FcRL5. While the phenotype and conditions leading to neogenesis of atypical MBCs in malaria-experienced individuals have been studied extensively, the origin of these cells remains equivocal. Functional similarities between FcRL5<jats:sup>+<\/jats:sup> atypical MBCs and FcRL5<jats:sup>+<\/jats:sup> classical MBCs have been reported, suggesting that these cells may be developmentally related.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Here, a longitudinal analysis of FcRL5 expression in various B cell subsets was performed in two children from a high transmission region in Uganda over a 6-month period in which both children experienced a malaria episode. Using B-cell receptor (BCR)-sequencing to track clonally related cells, the connections between IgM<jats:sup>+<\/jats:sup> and IgG<jats:sup>+<\/jats:sup> atypical MBCs and other B cell subsets were studied.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The highest expression of FcRL5 was found among IgG<jats:sup>+<\/jats:sup> atypical MBCs, but FcRL5<jats:sup>+<\/jats:sup> cells were present in all MBC subsets. Following malaria, FcRL5 expression increased in all IgM<jats:sup>+<\/jats:sup> MBC subsets analysed here: classical, activated, and atypical MBCs, while results for IgG<jats:sup>+<\/jats:sup> MBC subsets were inconclusive. IgM<jats:sup>+<\/jats:sup> atypical MBCs showed few connections with other B cell subsets, higher turnover than IgG<jats:sup>+<\/jats:sup> atypical MBCs, and were predominantly derived from na\u00efve B cells and FcRL5<jats:sup>\u2212<\/jats:sup> IgM<jats:sup>+<\/jats:sup> classical MBCs. In contrast, IgG<jats:sup>+<\/jats:sup> atypical MBCs were clonally expanded and connected with classical MBCs. IgG<jats:sup>+<\/jats:sup> atypical MBCs present after a malaria episode mainly originated from FcRL5<jats:sup>+<\/jats:sup> IgG<jats:sup>+<\/jats:sup> classical MBCs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Collectively, these results suggest fundamental differences between unswitched and class-switched B cell populations and provide clues about the primary developmental pathways of atypical MBCs in malaria-experienced individuals.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12936-021-03970-1","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T11:04:48Z","timestamp":1636542288000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Longitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria"],"prefix":"10.1186","volume":"20","author":[{"given":"S. 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Participants enrolled in this study were from the Nagongera sub-county in Tororo District, Uganda and have provided written consent for the use of their samples for research. The PRISM cohort study was approved by the Makerere University School of Medicine Research and Ethics Committee (SOMREC), London School of Hygiene and Tropical Medicine IRB, and the University of California, San Francisco Human Research Protection Program & IRB.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"435"}}