Yang Ming, Yi Ping, Jiang Jiao, Zhao Ming, Wu Haijing, Lu Qianjin
Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China.
Int Rev Immunol. 2023;42(1):1-25. doi: 10.1080/08830185.2021.1964498. Epub 2021 Aug 27.
B cells play a crucial role in antigen presentation, antibody production and pro-/anti-inflammatory cytokine secretion in adaptive immunity. Several translational factors including transcription factors and cytokines participate in the regulation of B cell development, with the cooperation of epigenetic regulations. Autoimmune diseases are generally characterized with autoreactive B cells and high-level pathogenic autoantibodies. The success of B cell depletion therapy in mouse model and clinical trials has proven the role of B cells in pathogenesis of autoimmune diseases. The failure of B cell tolerance in immune checkpoints results in accumulated autoreactive naïve B (B) cells with aberrant B cell receptor signaling and dysregulated B cell response, contributing to self-antibody-mediated autoimmune reaction. Dysregulation of translational factors and epigenetic alterations in B cells has been demonstrated to correlate with aberrant B cell compartment in autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren's syndrome, multiple sclerosis, diabetes mellitus and pemphigus. This review is intended to summarize the interaction of translational factors and epigenetic regulations that are involved with development and differentiation of B cells, and the mechanism of dysregulation in the pathogenesis of autoimmune diseases.
B细胞在适应性免疫中的抗原呈递、抗体产生以及促炎/抗炎细胞因子分泌过程中发挥着关键作用。包括转录因子和细胞因子在内的多种翻译因子，在表观遗传调控的协同作用下，参与B细胞发育的调节。自身免疫性疾病通常以自身反应性B细胞和高水平致病性自身抗体为特征。B细胞清除疗法在小鼠模型和临床试验中的成功，证明了B细胞在自身免疫性疾病发病机制中的作用。免疫检查点中B细胞耐受性的缺失，导致具有异常B细胞受体信号传导和失调B细胞反应的自身反应性幼稚B（B）细胞积累，从而引发自身抗体介导的自身免疫反应。已证明B细胞中翻译因子的失调和表观遗传改变与自身免疫性疾病（如系统性红斑狼疮、类风湿性关节炎、原发性干燥综合征、多发性硬化症、糖尿病和天疱疮）中异常的B细胞区室相关。本综述旨在总结参与B细胞发育和分化的翻译因子与表观遗传调控之间的相互作用，以及自身免疫性疾病发病机制中失调的机制。
