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Am J Transplant. 2019 Dec 7. doi: 10.1111/ajt.15737. [Epub ahead of print]

B cell clonal expansion within immune infiltrates in human cardiac allograft vasculopathy.

Author information

1
Center for Transplantation Science, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
2
Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
3
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
4
Transplant Center, The First Hospital of Jilin University, Changchun, China.
5
Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA.
6
Department of Pathology & Cell Biology, Columbia University Medical Center, New York, New York, USA.
7
Division of Cardiothoracic Surgery, Department of Surgery, Columbia University Medical Center, New York, New York, USA.
8
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
9
Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
10
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.

Abstract

Cardiac allograft vasculopathy (CAV) is associated with intragraft B cell infiltrates. Here, we studied the clonal composition of B cell infiltrates using 4 graft specimens with CAV. Using deep sequencing, we analyzed the immunoglobulin heavy chain variable region repertoire in both graft and blood. Results showed robust B cell clonal expansion in the graft but not in the blood for all cases. Several expanded B cell clones, characterized by their uniquely rearranged complementarity-determining region 3, were detected in different locations in the graft. Sequences from intragraft B cells also showed elevated levels of mutated rearrangements in the graft compared to blood B cells. The number of somatic mutations per rearrangement was also higher in the graft than in the blood, suggesting that B cells continued maturing in situ. Overall, our studies demonstrated B cell clonal expansion in human cardiac allografts with CAV. This local B cell response may contribute to the pathophysiology of CAV through a mechanism that needs to be identified.

KEYWORDS:

B cell biology; basic (laboratory) research/science; heart (allograft) function/dysfunction; heart transplantation/cardiology; immunobiology; rejection: chronic

PMID:
31811777
DOI:
10.1111/ajt.15737

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