Effects of the complement system on antibody formation and function: implications for transplantation.
Effects of the complement system on antibody formation and function: implications for transplantation.
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DOI：
10.1097/mot.0000000000001002
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发表时间：
2022-10-01
影响因子：
2.2
通讯作者：
Heeger, Peter S.
中科院分区：
文献类型：
--
作者：
Cumpelik, Arun;Heeger, Peter S.
在抗体介导的同种异体移植排斥中，供体反应性抗体部分通过补体激活引起移植损伤。新的机制见解表明补体还调节体液免疫反应的发展。在此，我们回顾了描述补体如何影响抗体形成的最新数据，并讨论了治疗意义。外渗 T 细胞与整合素相互作用，表达并激活细胞内补体，从而驱动对 CD4+ 辅助细胞至关重要的免疫代谢适应。边缘区 B 细胞可以通过补体依赖性吞噬作用从树突状细胞获得完整的主要组织相容性复合物，然后呈递给 T 细胞。生发中心 (GC) 中激活的 B 细胞接收来自 T 辅助细胞的共刺激信号。这些 GC B 细胞在表面补体调节剂表达中经历坐标变化，从而允许亲和力成熟所需的 GC B 细胞上的补体受体信号传导。积极选择的高亲和力 B 细胞可以分化为浆细胞，产生能够连接内皮细胞和移植细胞的供体 HLA 反应性抗体。随后的亚裂解补体攻击可以刺激内皮细胞激活 CD4+ 和 CD8+ T 细胞，促进细胞和体液排斥。新开发的补体抑制剂正在测试用于预防/治疗移植排斥。补体系统影响T细胞、B细胞和内皮细胞的活化，从而导致同种异体移植物损伤。针对补体激活的新兴治疗策略有可能预防或消除移植损伤并改善移植结果。
In antibody-mediated allograft rejection, donor-reactive antibodies cause transplant injury in part via complement activation. New mechanistic insights indicate complement also modulates development of humoral immune responses. Herein we review recent data that describes how complement affects antibody formation and we discuss therapeutic implications. Extravasating T-cells interacting with integrins express and activate intracellular complement that drives immune-metabolic adaptations vital for CD4+ helper cells. Marginal zone B cells can acquire intact major histocompatibility complexes from dendritic cells via complement-dependent trogocytosis for presentation to T cells. Activated B cells in germinal centers (GC) receive co-stimulatory signals from T helper cells. These GC B cells undergo coordinate shifts in surface complement regulator expression that permit complement receptor signaling on the GC B cells required for affinity maturation. The positively selected, high affinity B cells can differentiate into plasma cells that produce donor-HLA-reactive antibodies capable of ligating endothelial, among other, graft cells. Subsequent sub-lytic complement attack can stimulate endothelial cells to activate CD4+ and CD8+ T cells, promoting cellular and humoral rejection. Newly developed complement inhibitors are being tested to prevent/treat transplant rejection. The complement system influences T cell, B cell and endothelial cell activation, and thereby contributes allograft injury. Emerging therapeutic strategies targeting complement activation have the potential to prevent or abrogate transplant injury and improve transplant outcomes.