Service de Transplantation Rénale et d'Immunologie Clinique, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France.
Transpl Immunol. 2012 Mar;26(2-3):101-6. doi: 10.1016/j.trim.2011.11.003. Epub 2011 Nov 12.
Modern immunosuppressive armamentarium inadequately controls the humoral arm of recipient immune response, which in turn plays a central role in the pathogenesis of chronic rejection, a major cause of late allograft failure. A consensus sequence has progressively emerged from the integration of both experimental and clinical data, in which the binding of circulating donor-specific antibodies to mismatched HLA molecules expressed by graft microvasculature leads to chronic inflammation and progressive tissue destruction. Recent data suggest however that beyond their role in antibody production, B cells are also endowed with critical, yet overlooked, antibody-independent functions. Their abilities to present antigens and drive lymphoid neogenesis within rejected organ place them at the center of immune regulation with the power to enhance or inhibit antigraft immunity. The key challenges for the next few years will be to learn how these conceptual progresses can be translated into innovative B cell-targeting therapies to improve long-term allograft outcome.
现代免疫抑制武器库不能充分控制受者免疫反应的体液部分，而后者在慢性排斥反应的发病机制中起着核心作用，慢性排斥反应是移植物晚期失功的主要原因。通过整合实验和临床数据，逐渐出现了一个共识序列，其中循环供体特异性抗体与移植物微血管表达的错配 HLA 分子结合，导致慢性炎症和进行性组织破坏。然而，最近的数据表明，B 细胞除了在抗体产生中发挥作用外，还具有重要但被忽视的抗体非依赖性功能。它们提呈抗原和在被排斥的器官内驱动淋巴样新生的能力使它们处于免疫调节的中心，具有增强或抑制抗移植物免疫的能力。未来几年的关键挑战将是了解如何将这些概念进展转化为创新的 B 细胞靶向治疗方法，以改善长期移植物预后。
