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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Clinical Investigation
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675462/ https://www.ncbi.nlm.nih.gov/pubmed/36134664 http://dx.doi.org/10.1172/jci.insight.156648 |
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author | Smirnova, Natalia F. Riemondy, Kent Bueno, Marta Collins, Susan Suresh, Pavan Wang, Xingan Patel, Kapil N. Cool, Carlyne Königshoff, Melanie Sharma, Nirmal S. Eickelberg, Oliver |
author_facet | Smirnova, Natalia F. Riemondy, Kent Bueno, Marta Collins, Susan Suresh, Pavan Wang, Xingan Patel, Kapil N. Cool, Carlyne Königshoff, Melanie Sharma, Nirmal S. Eickelberg, Oliver |
author_sort | Smirnova, Natalia F. |
collection | PubMed |
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 IgG(2c) 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. |
format | Online Article Text |
id | pubmed-9675462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-96754622022-11-21 Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation Smirnova, Natalia F. Riemondy, Kent Bueno, Marta Collins, Susan Suresh, Pavan Wang, Xingan Patel, Kapil N. Cool, Carlyne Königshoff, Melanie Sharma, Nirmal S. Eickelberg, Oliver JCI Insight Resource and Technical Advance 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 IgG(2c) 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. American Society for Clinical Investigation 2022-09-22 /pmc/articles/PMC9675462/ /pubmed/36134664 http://dx.doi.org/10.1172/jci.insight.156648 Text en © 2022 Smirnova et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Resource and Technical Advance Smirnova, Natalia F. Riemondy, Kent Bueno, Marta Collins, Susan Suresh, Pavan Wang, Xingan Patel, Kapil N. Cool, Carlyne Königshoff, Melanie Sharma, Nirmal S. Eickelberg, Oliver Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung 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 | Resource and Technical Advance |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675462/ https://www.ncbi.nlm.nih.gov/pubmed/36134664 http://dx.doi.org/10.1172/jci.insight.156648 |
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