Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Renal and Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Immunol Rev. 2021 Jan;299(1):31-44. doi: 10.1111/imr.12933. Epub 2021 Jan 22.
Regulatory B cells (Bregs) ameliorate autoimmune disease and prevent allograft rejection. Conversely, they hinder effective clearance of pathogens and malignancies. Breg activity is mainly attributed to IL-10 expression, but also utilizes additional regulatory mechanisms such as TGF-β, FasL, IL-35, and TIGIT. Although Bregs are present in various subsets defined by phenotypic markers (including canonical B cell subsets), our understanding of Bregs has been limited by the lack of a broadly inclusive and specific phenotypic or transcriptional marker. TIM-1, a broad marker for Bregs first identified in transplant models, plays a major role in Breg maintenance and induction. Here, we expand on the role of TIM-1 Bregs in immune tolerance and propose TIM-1 as a unifying marker for Bregs that utilize various inhibitory mechanisms in addition to IL-10. Further, this review provides an in-depth assessment of our understanding of Bregs in transplantation as elucidated in murine models and clinical studies. These studies highlight the major contribution of Bregs in preventing allograft rejection, and their ability to serve as highly predictive biomarkers for clinical transplant outcomes.
调节性 B 细胞（Bregs）可减轻自身免疫性疾病并预防同种异体移植物排斥。相反，它们会阻碍对病原体和恶性肿瘤的有效清除。Breg 的活性主要归因于 IL-10 的表达，但也利用了其他调节机制，如 TGF-β、FasL、IL-35 和 TIGIT。尽管 Bregs 存在于各种表型标志物定义的亚群中（包括经典 B 细胞亚群），但由于缺乏广泛包容性和特异性的表型或转录标志物，我们对 Bregs 的理解受到了限制。TIM-1 是在移植模型中首次鉴定的 Bregs 的广谱标志物，在 Breg 的维持和诱导中起主要作用。在这里，我们扩展了 TIM-1+Bregs 在免疫耐受中的作用，并提出 TIM-1 作为一种统一的标志物，用于除了 IL-10 之外还利用各种抑制机制的 Bregs。此外，本综述深入评估了我们在小鼠模型和临床研究中对移植中 Bregs 的理解。这些研究强调了 Bregs 在预防同种异体移植物排斥中的重要作用，以及它们作为临床移植结果的高度预测性生物标志物的能力。
