The Janus face of proliferating plasmablasts in dengue and COVID-19 infections
IntroductionB 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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1068424/full |
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| author | Priya Nayak Kavitha Mukund Shankar Subramaniam Shankar Subramaniam Shankar Subramaniam |
| author_facet | Priya Nayak Kavitha Mukund Shankar Subramaniam Shankar Subramaniam Shankar Subramaniam |
| author_sort | Priya Nayak |
| collection | DOAJ |
| description | IntroductionB 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.MethodsWe 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.ResultsIn 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.DiscussionWe 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. |
| first_indexed | 2024-03-12T15:16:09Z |
| format | Article |
| id | doaj.art-956dbfa092be41c0a9e03b42b8af30bc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T15:16:09Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-956dbfa092be41c0a9e03b42b8af30bc2023-08-11T12:16:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.10684241068424The Janus face of proliferating plasmablasts in dengue and COVID-19 infectionsPriya Nayak0Kavitha Mukund1Shankar Subramaniam2Shankar Subramaniam3Shankar Subramaniam4Department of Bioengineering, University of California, San Diego, La Jolla, CA, United StatesDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, United StatesDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, United StatesDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, United StatesDepartment of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, United StatesIntroductionB 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.MethodsWe 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.ResultsIn 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.DiscussionWe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1068424/fullCOVID-19B-cellsdengueplasmablastsnaivememory |
| spellingShingle | Priya Nayak Kavitha Mukund Shankar Subramaniam Shankar Subramaniam Shankar Subramaniam The Janus face of proliferating plasmablasts in dengue and COVID-19 infections Frontiers in Immunology COVID-19 B-cells dengue plasmablasts naive memory |
| title | The Janus face of proliferating plasmablasts in dengue and COVID-19 infections |
| title_full | The Janus face of proliferating plasmablasts in dengue and COVID-19 infections |
| title_fullStr | The Janus face of proliferating plasmablasts in dengue and COVID-19 infections |
| title_full_unstemmed | The Janus face of proliferating plasmablasts in dengue and COVID-19 infections |
| title_short | The Janus face of proliferating plasmablasts in dengue and COVID-19 infections |
| title_sort | janus face of proliferating plasmablasts in dengue and covid 19 infections |
| topic | COVID-19 B-cells dengue plasmablasts naive memory |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1068424/full |
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