JCI Insight (Sep 2022)

Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation

  • 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

Journal volume & issue
Vol. 7, no. 18

Abstract

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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.

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