{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:55:59Z","timestamp":1787943359975,"version":"build-2784847793"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T00:00:00Z","timestamp":1691712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 LM012595, U19 AI090023, R01 HL108735, OT2 1 OD030544"],"award-info":[{"award-number":["R01 LM012595, U19 AI090023, R01 HL108735, OT2 1 OD030544"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>B cells play an integral role in the immune response to both dengue fever and COVID-19. Prior scRNAseq analyses of peripheral plasmablasts in COVID-19 have revealed a heterogeneous population with distinct cell subsets associated with proliferation; prior studies in patients with dengue fever have likewise shown the presence of proliferative pre-plasmablasts in the circulation. These findings may have implications for disease severity. In this study, we sought to gain a mechanistic understanding of the intracellular processes in naive and memory B cells that are associated with and may lead to an expanded proliferative plasmablast population in the circulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed age-controlled (pediatric and adult), peripheral blood mononuclear cell scRNAseq datasets from patients infected with either dengue (primary or secondary) or COVID-19 (non-severe or severe) from previously published studies. Our preliminary analysis showed that pediatric patients with dengue and adults with COVID-19 had an expanded proliferative plasmablast (p-PB) population. By contrast, neither the adults with dengue nor the children with COVID-19 in our dataset had p-PBs. We used this distinctive preliminary signature to guide our analyses design and expanded our analyses to naive and memory B cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In age\/disease conditions with and without p-PBs, we found differences in cell sensing and activation, including via the B cell receptor and downstream signal transduction. Likewise, inflammation was mediated differently: relative to groups without p-PBs, those with p-PBs had increased expression of interferon response and S100 genes (particularly severe COVID-19). Furthermore, several transcription factors at the nexus of activation, inflammation, and cell fate decisions were expressed differently in groups with and without p-PBs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We used dengue and COVID-19 infections in adult and pediatric patients (focusing on naive B, memory B, and plasmablast cells) as a model to better understand the mechanisms that may give rise to p-PB populations in the circulation. Our results indicate that a more pro-inflammatory state in naive and memory B cells correlated with - and could influence the generation of- proliferating plasmablasts. Further exploration of these mechanisms will have implications for immune memory, vaccine development, and post-viral autoimmune syndromes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1068424","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T12:17:05Z","timestamp":1691756225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The Janus face of proliferating plasmablasts in dengue and COVID-19 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