@article{b59bdde70e0548bca6c8018498e4518b,
title = "A B cell–dependent pathway drives chronic lung allograft rejection after ischemia–reperfusion injury in mice",
abstract = "Chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplant (LT). Ischemia–reperfusion injury (IRI) promotes chronic rejection (CR) and CLAD, but the underlying mechanisms are not well understood. To examine mechanisms linking IRI to CR, a mouse orthotopic LT model using a minor alloantigen strain mismatch (C57BL/10 [B10, H-2b] → C57BL/6 [B6, H-2b]) and isograft controls (B6→B6) was used with antecedent minimal or prolonged graft storage. The latter resulted in IRI with subsequent airway and parenchymal fibrosis in prolonged storage allografts but not isografts. This pattern of CR after IRI was associated with the formation of B cell–rich tertiary lymphoid organs within the grafts and circulating autoantibodies. These processes were attenuated by B cell depletion, despite preservation of allograft T cell content. Our observations suggest that IRI may promote B cell recruitment that drives CR after LT. These observations have implications for the mechanisms leading to CLAD after LT.",
keywords = "B cell biology, animal models: murine, basic (laboratory) research/science, bronchiolitis obliterans (BOS), immunobiology, immunosuppression/immune modulation, innate immunity, lung (allograft) function/dysfunction, lung transplantation/pulmonology",
author = "Tatsuaki Watanabe and Tereza Martinu and Andrzej Chruscinski and Kristen Boonstra and Betty Joe and Miho Horie and Zehong Guan and Bei, {Ke Fan} and Hwang, {David M.} and Mingyao Liu and Shaf Keshavjee and Juvet, {Stephen C.}",
note = "Funding Information: Funding Information This research was supported by an Ontario Thoracic Society Grant-in-Aid (to Dr Juvet), a Multiorgan Transplant Program/Astellas Canada Research Grant (to Drs Juvet and Martinu) and by the Research Fellowship of the Uehara Memorial Foundation (to Dr Watanabe), the Pfizer Fellowship of the Japanese Respiratory Foundation (to Dr Watanabe), and a Cystic Fibrosis Canada Research Fellowship (to Dr Watanabe). Dr Horie was supported by a research training grant from Canon Medical Systems. The authors thank Jerome Valero and Paul Chartrand for laboratory management. We also acknowledge Chihiro Konoeda, Ei Miyamoto, Matthew White, Allen Duong, and Sajad Moshkelgosha for assistance with mouse experiments, TLO assessments, and flow cytometry. We thank Maor Epstein for assistance with analysis of antigen microarray data. This research was supported by an Ontario Thoracic Society Grant-in-Aid (to Dr Juvet), a Multiorgan Transplant Program/Astellas Canada Research Grant (to Drs Juvet and Martinu) and by the Research Fellowship of the Uehara Memorial Foundation (to Dr Watanabe), the Pfizer Fellowship of the Japanese Respiratory Foundation (to Dr Watanabe), and a Cystic Fibrosis Canada Research Fellowship (to Dr Watanabe). Dr Horie was supported by a research training grant from Canon Medical Systems. Publisher Copyright: {\textcopyright} 2019 The American Society of Transplantation and the American Society of Transplant Surgeons",
year = "2019",
month = dec,
day = "1",
doi = "10.1111/ajt.15550",
language = "English",
volume = "19",
pages = "3377--3389",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "12",
}