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.
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
Usage data is cumulative from March 2023 through March 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 1,517 | 528 |
207 | 152 | |
Figure | 391 | 7 |
Table | 18 | 0 |
Supplemental data | 69 | 11 |
Citation downloads | 67 | 0 |
Totals | 2,269 | 698 |
Total Views | 2,967 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.