Dysregulated translational factors and epigenetic regulations orchestrate in B cells contributing to autoimmune diseases

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.

Authors’ contributions

MY wrote the manuscript. PY, JJ and MZ conducted editing, and HJW and QJL revised the manuscript.

Declaration of interest

Authors declare that they have no conflict of interests.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 81830097, 81972943 and 81773332), Hunan Talent Young Investigator (No. 2019RS2012), Hunan Outstanding Young Investigator (No. 2020JJ2055) and CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2019-I2M-5-033).