Integrated analyses uncover new features of atypical memory B cells and novel targets for intervention
Background: Atypical memory B (AMB) is a novel subset of B lymphocytes, but its immune features and pathogenetic roles in systemic rheumatic diseases are still largely elusive. This study aimed to characterize transcriptomic features, immune phenotypes and potential signaling pathways of AMB, and al...
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| Format: | Article |
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Elsevier
2025-03-01
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| Series: | Immunobiology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171298525000117 |
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| author | Fuli Fan Shubei Liu Bin Wang Xiaojian Song Wei Wang |
| author_facet | Fuli Fan Shubei Liu Bin Wang Xiaojian Song Wei Wang |
| author_sort | Fuli Fan |
| collection | DOAJ |
| description | Background: Atypical memory B (AMB) is a novel subset of B lymphocytes, but its immune features and pathogenetic roles in systemic rheumatic diseases are still largely elusive. This study aimed to characterize transcriptomic features, immune phenotypes and potential signaling pathways of AMB, and also to confirm its alternations in systemic rheumatic diseases via combined transcriptome analyses. Method: B cell subsets and their transcriptomic signatures were identified via analyses of single cell RNA-sequencing (scRNA-seq) data. Functional characterization of AMB was performed with bioinformatics and CyTOF-based phenotyping. Alternation of AMB in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SjS) was evaluated via bioinformatic approaches. Result: A total of 11 B cell subsets including AMB were identified through scRNA-seq transcriptome analyses. Both transcriptome analyses and CyTOF-based immune phenotyping confirmed that AMB had increased levels of TBX21 (T-bet), ITGAX (CD11c), CD19, CD20 and CXCR3 (P < 0.05), and it had decreased expressions of CD27, CD38, CXCR4, CXCR5 and CD62L (P < 0.05). More than 50 % of T-bet+ B cells did not express CD11c, and more than 30 % expressed CD27. AMB was characterized by activated mTORC1 signaling and increased p-P38 level (P < 0.05). AMB transcriptional signature was significantly enriched in the peripheral blood and disease tissues of patients of SLE, RA and SjS (P < 0.05), suggesting the expanded AMB cells in those patients. Conclusion: This study defines the transcriptomic signature, immune phenotypes and potential signaling pathways of AMB, and also confirms the involvement of AMB in systemic rheumatic diseases including SLE, RA and SjS via transcriptomic approaches. mTORC1 signaling and P38/MAPK signaling are promising therapeutic targets for systemic rheumatic diseases mediated by AMB. |
| format | Article |
| id | doaj-art-72c5c914f75b4d3c80a1f038b77f541b |
| institution | Kabale University |
| issn | 0171-2985 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Immunobiology |
| spelling | doaj-art-72c5c914f75b4d3c80a1f038b77f541b2025-02-12T05:30:23ZengElsevierImmunobiology0171-29852025-03-012302152877Integrated analyses uncover new features of atypical memory B cells and novel targets for interventionFuli Fan0Shubei Liu1Bin Wang2Xiaojian Song3Wei Wang4Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266000, ChinaDepartment of Rheumatology and Immunology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, ChinaCentral Laboratory, Weifang People's Hospital, Shandong Second Medical University, Weifang 261000, China; Department of Traumatology and Orthopaedics, Weifang People's Hospital, Shandong Second Medical University, Weifang 261000, China; Corresponding author at: Department of Traumatology and Orthopaedics, Weifang People's Hospital, Shandong Second Medical University, Weifang 261000, China.Weiriver Novel Research Association, Weifang 262212, ChinaDepartment of Hematology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266000, China; Corresponding author.Background: Atypical memory B (AMB) is a novel subset of B lymphocytes, but its immune features and pathogenetic roles in systemic rheumatic diseases are still largely elusive. This study aimed to characterize transcriptomic features, immune phenotypes and potential signaling pathways of AMB, and also to confirm its alternations in systemic rheumatic diseases via combined transcriptome analyses. Method: B cell subsets and their transcriptomic signatures were identified via analyses of single cell RNA-sequencing (scRNA-seq) data. Functional characterization of AMB was performed with bioinformatics and CyTOF-based phenotyping. Alternation of AMB in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SjS) was evaluated via bioinformatic approaches. Result: A total of 11 B cell subsets including AMB were identified through scRNA-seq transcriptome analyses. Both transcriptome analyses and CyTOF-based immune phenotyping confirmed that AMB had increased levels of TBX21 (T-bet), ITGAX (CD11c), CD19, CD20 and CXCR3 (P < 0.05), and it had decreased expressions of CD27, CD38, CXCR4, CXCR5 and CD62L (P < 0.05). More than 50 % of T-bet+ B cells did not express CD11c, and more than 30 % expressed CD27. AMB was characterized by activated mTORC1 signaling and increased p-P38 level (P < 0.05). AMB transcriptional signature was significantly enriched in the peripheral blood and disease tissues of patients of SLE, RA and SjS (P < 0.05), suggesting the expanded AMB cells in those patients. Conclusion: This study defines the transcriptomic signature, immune phenotypes and potential signaling pathways of AMB, and also confirms the involvement of AMB in systemic rheumatic diseases including SLE, RA and SjS via transcriptomic approaches. mTORC1 signaling and P38/MAPK signaling are promising therapeutic targets for systemic rheumatic diseases mediated by AMB.http://www.sciencedirect.com/science/article/pii/S0171298525000117Atypical memory B cellsSystemic rheumatic diseasesSingle cell RNA-sequencingTreatment targets |
| spellingShingle | Fuli Fan Shubei Liu Bin Wang Xiaojian Song Wei Wang Integrated analyses uncover new features of atypical memory B cells and novel targets for intervention Immunobiology Atypical memory B cells Systemic rheumatic diseases Single cell RNA-sequencing Treatment targets |
| title | Integrated analyses uncover new features of atypical memory B cells and novel targets for intervention |
| title_full | Integrated analyses uncover new features of atypical memory B cells and novel targets for intervention |
| title_fullStr | Integrated analyses uncover new features of atypical memory B cells and novel targets for intervention |
| title_full_unstemmed | Integrated analyses uncover new features of atypical memory B cells and novel targets for intervention |
| title_short | Integrated analyses uncover new features of atypical memory B cells and novel targets for intervention |
| title_sort | integrated analyses uncover new features of atypical memory b cells and novel targets for intervention |
| topic | Atypical memory B cells Systemic rheumatic diseases Single cell RNA-sequencing Treatment targets |
| url | http://www.sciencedirect.com/science/article/pii/S0171298525000117 |
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