Columbia Center for Translational Immunology, New York Presbyterian Hospital, Columbia University Medical Center, New York, New York, USA.
Curr Opin Organ Transplant. 2019 Feb;24(1):31-36. doi: 10.1097/MOT.0000000000000591.
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.
B 细胞最近已成为实体器官排斥反应（尤其是心脏移植后慢性排斥反应——心脏移植后血管病）中的重要免疫细胞。B 细胞可发挥调节或效应功能。本综述将提供心脏移植后血管病中效应 B 细胞的最新信息。
独立研究报道了 B 细胞在心脏移植后血管病中的移植物浸润中丰富，特别是在冠状动脉周围。浸润物包含 CD20+CD27+记忆 B 细胞和分化的 CD20-CD138+浆细胞，这些细胞几乎总是与 T 细胞和巨噬细胞相关。其中一些浸润物的结构使人联想到生发中心，提示在移植物中产生三级淋巴器官。值得注意的是，在循环供体人类白细胞抗原特异性抗体缺失的情况下，通常会检测到 B 细胞浸润，这强烈表明这两个成分无关。从心脏移植浸润物中分离的 B 细胞克隆的特征揭示了先天多反应性 B1 样 B 细胞的普遍性。越来越多的证据表明，这些细胞主要作为原位抗原提呈细胞发挥作用。还考虑了其他效应功能，如局部抗体分泌和促炎细胞因子产生，促进 T 细胞极化、巨噬细胞激活和纤维化。
动物和人类研究的综合观察结果为心脏移植后血管病的 B 细胞效应器作用提供了实质性支持。基于这些综合发现，针对 B 细胞的治疗策略可以合理地设想用于预防或治疗这种并发症。
