Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands.
Int J Immunogenet. 2020 Jun;47(3):227-234. doi: 10.1111/iji.12493. Epub 2020 May 10.
Humoral alloimmunity mediated by anti-human leucocyte antigen (HLA) antibodies is a major challenge in kidney transplantation and impairs the longevity of the transplanted organ. The immunological risk of an individual patient is currently mainly assessed by detection of HLA antibodies in the serum, which are produced by long-lived bone marrow-residing plasma cells. However, humoral alloimmunity is complex, and alloreactive memory B cells constitute an additional factor in the interplay of immune cells. These recirculating "silent" cells are responsible for the immunological recall response by differentiating into antibody-producing cells upon antigen re-encounter. Historically, due to the lack of appropriate and routinely applicable assays to determine the presence and HLA specificity of alloreactive memory B cells, their contribution to the humoral alloimmune response has clinically often been suspected but could not be determined. In this review, we give an overview of recent advances in techniques to detect alloreactive memory B cells and discuss their strengths and limitations. Furthermore, we summarize experiences with these techniques in alloimmunized individuals and transplant recipients, thereby emphasizing unmet needs to be addressed in future studies.
体液性同种异体免疫由抗人类白细胞抗原（HLA）抗体介导，是肾移植的主要挑战，会损害移植器官的长期功能。个体患者的免疫风险目前主要通过检测血清中的 HLA 抗体来评估，这些抗体是由长寿的骨髓定居浆细胞产生的。然而，体液性同种异体免疫很复杂，同种反应性记忆 B 细胞是免疫细胞相互作用的另一个因素。这些循环的“沉默”细胞在再次遇到抗原时分化为产生抗体的细胞，负责免疫记忆反应。从历史上看，由于缺乏适当和常规适用的检测方法来确定同种反应性记忆 B 细胞的存在和 HLA 特异性，它们对体液性同种免疫反应的贡献在临床上常常受到怀疑，但无法确定。在这篇综述中，我们概述了检测同种反应性记忆 B 细胞的最新技术进展，并讨论了它们的优缺点。此外，我们总结了这些技术在免疫致敏个体和移植受者中的应用经验，从而强调了未来研究中需要解决的未满足需求。
