Institute of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria.
Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck 6020, Austria.
Exp Gerontol. 2020 Sep;138:110985. doi: 10.1016/j.exger.2020.110985. Epub 2020 Jun 3.
The uniqueness of each B cell lies in the structural diversity of the B-cell antigen receptor allowing the virtually limitless recognition of antigens, a necessity to protect individuals against a range of challenges. B-cell development and response to stimulation are exquisitely regulated by a group of cell surface receptors modulating various signaling cascades and their associated genetic programs. The effects of these signaling pathways in optimal antibody-mediated immunity or the aberrant promotion of immune pathologies have been intensely researched in the past in young individuals. In contrast, we are only beginning to understand the contribution of these pathways to the changes in B cells of old organisms. Thus, critical transcription factors such as E2A and STAT5 show differential expression or activity between young and old B cells. As a result, B-cell physiology appears altered, and antibody production is impaired. Here, we discuss selected phenotypic changes during B-cell aging and attempt to relate them to alterations of molecular mechanisms.
每个 B 细胞的独特性在于 B 细胞抗原受体的结构多样性,这种多样性允许对抗原进行几乎无限的识别,这是保护个体免受各种挑战的必要条件。B 细胞的发育和对刺激的反应受到一组细胞表面受体的精细调节,这些受体调节各种信号级联及其相关的遗传程序。在过去,人们对这些信号通路在最佳抗体介导的免疫或免疫病理的异常促进中的作用进行了深入研究。相比之下,我们才刚刚开始了解这些途径对老年生物体内 B 细胞变化的贡献。因此,E2A 和 STAT5 等关键转录因子在年轻和老年 B 细胞之间表现出不同的表达或活性。结果,B 细胞的生理学似乎发生了改变,抗体的产生受到了损害。在这里,我们讨论 B 细胞衰老过程中的一些表型变化,并试图将其与分子机制的改变联系起来。