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Effector B cells in cardiac allograft vasculopathy

Zorn, Emmanuel

Current Opinion in Organ Transplantation: February 2019 - Volume 24 - Issue 1 - p 31–36
doi: 10.1097/MOT.0000000000000591
TRANSPLANT IMMUNOLOGY: REJECTION, TOLERANCE AND HISTOCOMPATIBILITY: Edited by Paolo Cravedi
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Purpose of review B cells have recently emerged as important immune players in solid organ rejection, especially in cardiac allograft vasculopathy (CAV), a chronic form of rejection following heart transplantation. B cells can exert either regulatory or effector functions. This review will provide an update on effector B cells in CAV.

Recent findings Independent studies reported the abundance of B cells in graft infiltrates during CAV, especially around coronary arteries. Infiltrates comprise CD20+ CD27+ memory B cells together with differentiated CD20−CD138+ plasma cells, which are almost always associated with T cells and macrophages. The structure of some of these infiltrates evokes that of germinal centers, suggesting the generation of tertiary lymphoid organs in the graft. Remarkably, B-cell infiltrates are most often detected in the absence of circulating donor human leukocyte antigen-specific antibodies, strongly suggesting that the two components are unrelated. Characterization of B-cell clones isolated from explanted human cardiac graft infiltrates revealed the prevalence of polyreactive innate, B1-like B cells. Accumulating evidence suggests that these cells act primarily as antigen-presenting cells in situ. Additional effector functions, such as local antibody secretion and pro-inflammatory cytokine production, promoting T-cell polarization, macrophage activation and fibrosis are also considered.

Summary Converging observations made through animal and human studies add substantial support for an effector B-cell role in the pathophysiology of CAV. On the basis of these collective findings, a therapeutic strategy targeting B cells could reasonably be envisaged to prevent or treat this complication.

Columbia Center for Translational Immunology, New York Presbyterian Hospital, Columbia University Medical Center, New York, New York, USA

Correspondence to Emmanuel Zorn, PhD, Columbia Center for Translational Immunology, New York Presbyterian Hospital, Columbia University Medical Center, 630 West 168th Street, Black Building, Mailbox 127, New York, NY 10032, USA. Tel: +1 212 342 3453; e-mail: ez2184@cumc.columbia.edu

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