Prevalence of polyreactive innate clones among graft-infiltrating B cells in human cardiac allograft vasculopathy

Chatterjee, Debanjana; Moore, Carolina; Gao, Baoshan; Clerkin, Kevin J.; See, Sarah B.; Shaked, David; Rogers, Kortney; Nunez, Sarah; Veras, Yokarla; Addonizio, Linda; Givertz, Michael M.; Naka, Yoshifumi; Mancini, Donna; Vasilescu, Rodica; Marboe, Charles; et. al.


BACKGROUND: Cardiac allograft vasculopathy (CAV) has been associated with graft-infiltrating B cells, although their characteristics are still unclear. In this study we examined the frequency, localization and reactivity profile of graft-infiltrating B cells to determine their contribution to the pathophysiology of CAV. METHODS: B cells, plasma cells and macrophages were examined by immunohistochemistry in 56 allografts with CAV, 49 native failed hearts and 25 autopsy specimens. A total of 102 B-cell clones were immortalized directly from the infiltrates of 3 fresh cardiac samples with CAV. Their secreted antibodies were assessed using enzyme-linked immunoassay and flow cytometry. RESULTS: B-cell infiltration was observed around coronary arteries in 93% of allograft explants with CAV. Comparatively, intragraft B cells were less frequent and less dense in the intraventricular myocardium from where routine biopsies are obtained. Plasma cells and macrophages were also detected in 85% and 95% of explants, respectively. Remarkably, B-cell infiltrates were not associated with circulating donor-specific antibodies (DSA) or prior episodes of antibody-mediated rejection (AMR). Among all B-cell clones generated from 3 explants with CAV, a majority secreted natural antibodies reactive to multiple autoantigens and apoptotic cells, a characteristic of innate B cells. CONCLUSIONS: Our study reveals a high frequency of infiltrating B cells around the coronary arteries of allografts with CAV, independent of DSA or AMR. These cells are enriched for innate B cells with a polyreactive profile. The findings shift the focus from conventional DSA-producing B cells to the potentially pathogenic polyreactive B cells in the development of clinical CAV. (C) 2018 International Society for Heart and Lung Transplantation. All rights reserved.

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Título según WOS: ID WOS:000427400800012 Not found in local WOS DB
Volumen: 37
Número: 3
Editorial: Elsevier Science Inc.
Fecha de publicación: 2018
Página de inicio: 385
Página final: 393


Notas: ISI