Effector B cells in cardiac allograft vasculopathy.

Abstract

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. 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. 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.