Section of Transplantation, Department of Surgery, University of Chicago, Chicago, IL, United States.
Cell Immunol. 2020 Mar;349:104061. doi: 10.1016/j.cellimm.2020.104061. Epub 2020 Feb 7.
Transplantation of fully allogeneic organs into immunocompetent recipients invariably elicits T cell and B cell responses that lead to the production of donor-specific antibodies (DSA). When immunosuppression is inadequate donor-specific T cell and B cell responses escape, leading to T cell-mediated rejection (TCMR), antibody mediated (ABMR) rejection, or mixed rejection (MR) exhibiting features of both TCMR and ABMR. Current literature suggests that ABMR is a major cause of late graft loss, and that new therapies to curtail the donor-specific humoral response are necessary. The majority of research into B cell responses elicited by allogeneic allografts in both preclinical models and clinical studies, has focused on the function of B cells as antibody-secreting cells and the pathogenic effects of DSA as mediators of ABMR. However, it has long been recognized that the DSA response to allografts is T cell-dependent, and that B cells engage in cognate interactions with T cells that provide "help" and promote B cell differentiation into antibody-secreting cells (ASCs). This review focusses the function of B cells as antigen-presenting cells (APCs) to T cells in lymphoid organs, how they may be critical APCs to T cell in the allograft, and the functional consequences of these interactions.
将完全同种异体器官移植到免疫功能正常的受者中,总会引起 T 细胞和 B 细胞反应,导致产生供体特异性抗体 (DSA)。当免疫抑制不足时,供体特异性 T 细胞和 B 细胞反应会逃逸,导致 T 细胞介导的排斥反应 (TCMR)、抗体介导的排斥反应 (ABMR)或混合排斥反应 (MR),表现出 TCMR 和 ABMR 的特征。目前的文献表明,ABMR 是晚期移植物丢失的主要原因,需要新的治疗方法来抑制供体特异性体液反应。在临床前模型和临床研究中,大多数关于同种异体移植物引起的 B 细胞反应的研究都集中在 B 细胞作为抗体分泌细胞的功能和 DSA 作为 ABMR 介质的致病作用上。然而,人们早就认识到,同种异体移植物的 DSA 反应是 T 细胞依赖性的,B 细胞与 T 细胞发生同源相互作用,提供“帮助”并促进 B 细胞分化为抗体分泌细胞 (ASCs)。这篇综述重点介绍了 B 细胞作为淋巴器官中 T 细胞的抗原呈递细胞 (APC)的功能,它们如何成为同种异体移植物中 T 细胞的关键 APC,以及这些相互作用的功能后果。