Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation
Bronchiolitis obliterans syndrome (BOS) is the main reason for poor outcomes after lung transplantation (LTx). We and others have recently identified B cells as major contributors to BOS after LTx. The extent of B cell heterogeneity and the relative contributions of B cell subpopulations to BOS, how...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-09-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.156648 |
| _version_ | 1797634377317875712 |
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| author | Natalia F. Smirnova Kent Riemondy Marta Bueno Susan Collins Pavan Suresh Xingan Wang Kapil N. Patel Carlyne Cool Melanie Königshoff Nirmal S. Sharma Oliver Eickelberg |
| author_facet | Natalia F. Smirnova Kent Riemondy Marta Bueno Susan Collins Pavan Suresh Xingan Wang Kapil N. Patel Carlyne Cool Melanie Königshoff Nirmal S. Sharma Oliver Eickelberg |
| author_sort | Natalia F. Smirnova |
| collection | DOAJ |
| description | Bronchiolitis obliterans syndrome (BOS) is the main reason for poor outcomes after lung transplantation (LTx). We and others have recently identified B cells as major contributors to BOS after LTx. The extent of B cell heterogeneity and the relative contributions of B cell subpopulations to BOS, however, remain unclear. Here, we provide a comprehensive analysis of cell population changes and their gene expression patterns during chronic rejection after orthotopic LTx in mice. Of 11 major cell types, Mzb1-expressing plasma cells (PCs) were the most prominently increased population in BOS lungs. These findings were validated in 2 different cohorts of human BOS after LTx. A Bhlhe41, Cxcr3, and Itgb1 triple-positive B cell subset, also expressing classical markers of the innate-like B-1 B cell population, served as the progenitor pool for Mzb1+ PCs. This subset accounted for the increase in IgG2c production within BOS lung grafts. A genetic lack of Igs decreased BOS severity after LTx. In summary, we provide a detailed analysis of cell population changes during BOS. IgG+ PCs and their progenitors — an innate B cell subpopulation — are the major source of local Ab production and a significant contributor to BOS after LTx. |
| first_indexed | 2024-03-11T12:07:52Z |
| format | Article |
| id | doaj.art-96c9037e12a14bf89a9c5ed4e05661c0 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:07:52Z |
| publishDate | 2022-09-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-96c9037e12a14bf89a9c5ed4e05661c02023-11-07T16:24:35ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-09-01718Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantationNatalia F. SmirnovaKent RiemondyMarta BuenoSusan CollinsPavan SureshXingan WangKapil N. PatelCarlyne CoolMelanie KönigshoffNirmal S. SharmaOliver EickelbergBronchiolitis obliterans syndrome (BOS) is the main reason for poor outcomes after lung transplantation (LTx). We and others have recently identified B cells as major contributors to BOS after LTx. The extent of B cell heterogeneity and the relative contributions of B cell subpopulations to BOS, however, remain unclear. Here, we provide a comprehensive analysis of cell population changes and their gene expression patterns during chronic rejection after orthotopic LTx in mice. Of 11 major cell types, Mzb1-expressing plasma cells (PCs) were the most prominently increased population in BOS lungs. These findings were validated in 2 different cohorts of human BOS after LTx. A Bhlhe41, Cxcr3, and Itgb1 triple-positive B cell subset, also expressing classical markers of the innate-like B-1 B cell population, served as the progenitor pool for Mzb1+ PCs. This subset accounted for the increase in IgG2c production within BOS lung grafts. A genetic lack of Igs decreased BOS severity after LTx. In summary, we provide a detailed analysis of cell population changes during BOS. IgG+ PCs and their progenitors — an innate B cell subpopulation — are the major source of local Ab production and a significant contributor to BOS after LTx.https://doi.org/10.1172/jci.insight.156648PulmonologyTransplantation |
| spellingShingle | Natalia F. Smirnova Kent Riemondy Marta Bueno Susan Collins Pavan Suresh Xingan Wang Kapil N. Patel Carlyne Cool Melanie Königshoff Nirmal S. Sharma Oliver Eickelberg Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation JCI Insight Pulmonology Transplantation |
| title | Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation |
| title_full | Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation |
| title_fullStr | Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation |
| title_full_unstemmed | Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation |
| title_short | Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation |
| title_sort | single cell transcriptome mapping identifies a local innate b cell population driving chronic rejection after lung transplantation |
| topic | Pulmonology Transplantation |
| url | https://doi.org/10.1172/jci.insight.156648 |
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