Department of Medicine, Division of Rheumatology, Emory University, Atlanta, GA, USA.
Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.
Immunol Rev. 2019 Nov;292(1):76-89. doi: 10.1111/imr.12820. Epub 2019 Nov 22.
The maintenance of immunological tolerance of B lymphocytes is a complex and critical process that must be implemented as to avoid the detrimental development of autoreactivity and possible autoimmunity. Murine models have been invaluable to elucidate many of the key components in B-cell tolerance; however, translation to human homeostatic and pathogenic immune states can be difficult to assess. Functional autoreactive, flow cytometric, and single-cell cloning assays have proven to be critical in deciphering breaks in B-cell tolerance within autoimmunity; however, newer approaches to assess human B-cell tolerance may prove to be vital in the further exploration of underlying tolerance defects. In this review, we supply a comprehensive overview of human immune tolerance checkpoints with associated mechanisms of enforcement, and highlight current and future methodologies which are likely to benefit future studies into the mechanisms that become defective in human autoimmune conditions.
B 淋巴细胞免疫耐受的维持是一个复杂而关键的过程，必须加以实施，以避免自身反应性的有害发展和可能的自身免疫。鼠模型对于阐明 B 细胞耐受中的许多关键成分非常有价值；然而，将其转化为人类体内的稳态和致病性免疫状态可能难以评估。功能自身反应性、流式细胞术和单细胞克隆分析已被证明在破译自身免疫中的 B 细胞耐受中断方面非常重要；然而，评估人类 B 细胞耐受的新方法可能对于进一步探索潜在的耐受缺陷至关重要。在这篇综述中，我们提供了一个与执行相关机制的人类免疫耐受检查点的全面概述，并强调了当前和未来的方法，这些方法可能有益于未来对人类自身免疫疾病中出现缺陷的机制的研究。
