Division of Medicine, University College London, London, UK.
UCL Centre for Nephrology, Royal Free Hospital, London, UK.
Nat Rev Nephrol. 2019 Jan;15(1):11-26. doi: 10.1038/s41581-018-0074-7.
B cells have a central role in many autoimmune diseases, including in those with renal involvement, as well as in the immunological response to kidney transplantation. The majority of B cell studies have focused on their pathological role as antibody producers. However, these cells have broad functions in immune responses beyond immunoglobulin secretion, including antigen presentation to T cells and cytokine production. Importantly, not all B cell subsets enhance immune responses. Regulatory B (B) cells attenuate inflammation and contribute to the maintenance of immune tolerance. B cells are numerically deficient and/or dysfunctional in several autoimmune diseases that can affect the kidneys, including systemic lupus erythematosus and anti-neutrophil cytoplasmic antibody-associated vasculitis, as well as in some groups of renal transplant recipients with alloimmune graft damage. B cell-targeting biologics have been trialled with promising results in diverse immune-mediated renal conditions. These therapies can affect both pro-inflammatory B cells and B cells, potentially limiting their long-term efficacy. Future strategies might involve the modulation of pro-inflammatory B cells in combination with the stimulation of regulatory subsets. Additionally, the monitoring of individual B cell subsets in patients may lead to the discovery of novel biomarkers that could help to predict disease relapse or progression.
B 细胞在许多自身免疫性疾病中具有核心作用,包括伴有肾脏受累的自身免疫性疾病,以及肾移植的免疫反应。大多数 B 细胞研究都集中在其作为抗体产生细胞的病理作用上。然而,这些细胞在免疫反应中的功能广泛,除了免疫球蛋白分泌之外,还包括抗原呈递给 T 细胞和细胞因子的产生。重要的是,并非所有 B 细胞亚群都增强免疫反应。调节性 B(B)细胞可减弱炎症反应,并有助于维持免疫耐受。在几种可能影响肾脏的自身免疫性疾病中,B 细胞数量减少和/或功能障碍,包括系统性红斑狼疮和抗中性粒细胞胞质抗体相关性血管炎,以及一些伴有同种免疫移植物损伤的肾移植受者群体。针对 B 细胞的生物制剂已在多种免疫介导的肾脏疾病中进行了试验,结果令人鼓舞。这些疗法可同时影响促炎 B 细胞和 B 细胞,从而限制其长期疗效。未来的策略可能涉及调节促炎 B 细胞与刺激调节性亚群相结合。此外,监测患者的单个 B 细胞亚群可能会发现有助于预测疾病复发或进展的新型生物标志物。