Abstract

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_N) 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.

摘要

B 细胞在适应性免疫中的抗原呈递、抗体产生和促/抗炎细胞因子分泌中起着至关重要的作用。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配合下参与 B 细胞发育的调控。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 细胞耗竭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 细胞耐受性的失败导致累积的自身反应性幼稚 B (B _N) 具有异常 B 细胞受体信号和 B 细胞反应失调的细胞，有助于自身抗体介导的自身免疫反应。B 细胞中翻译因子的失调和表观遗传改变已被证明与自身免疫性疾病中的异常 B 细胞区室相关，例如系统性红斑狼疮、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。本综述旨在总结参与B细胞发育和分化的翻译因子和表观遗传调控的相互作用，以及自身免疫性疾病发病机制中失调的机制。