近日，美国埃默里大学Jeremy M. Boss和Iñaki Sanz研究组合作揭示了系统性红斑狼疮病人中B细胞功能紊乱的表观重编程。该研究于2019年8月发表于国际学术期刊《自然—免疫学》上。

研究人员分析了来自于人类五个B细胞亚群的DNA甲基化组、染色体开放程度以及转录组，其中包括来自于SLE患者及健康人群的最近定义的效应B细胞亚群。研究人员定义了这些亚群的分化阶级，并阐明了效应B细胞与记忆B细胞在表观遗传和转录组上的区别。重要的是，SLE的一个分子特征在静息态的初始细胞中已经建立，并在AP-1和EGR转录因子的模体处富集了开放的染色质。总而言之，这些因子与T-BET一起协同地改变了SLE病人中效应B细胞亚群的表观组。因此，这些发现定义了SLE病人中病理性B细胞功能紊乱的分子基础。

据悉，系统性红斑狼疮（SLE）的特征是来自于新激活初始细胞的病理性滤泡外B细胞的扩增。尽管这些细胞表达不同的标志物，其表观遗传结构以及如何促进SLE仍然知之甚少。

附：英文原文

Title: Epigenetic programming underpins B cell dysfunction in human SLE

Author: Christopher D. Scharer, Emily L. Blalock, Tian Mi, Benjamin G. Barwick, Scott A. Jenks, Tsuneo Deguchi, Kevin S. Cashman, Bridget E. Neary, Dillon G. Patterson, Sakeenah L. Hicks, Arezou Khosroshahi, F. Eun-Hyung Lee, Chungwen Wei, Iñaki Sanz, Jeremy M. Boss

Issue&Volume: Volume 20，Issue 8

Abstract: Systemic lupus erythematosus (SLE) is characterized by the expansion of extrafollicular pathogenic B cells derived from newly activated naive cells. Although these cells express distinct markers, their epigenetic architecture and how it contributes to SLE remain poorly understood. To address this, we determined the DNA methylomes, chromatin accessibility profiles and transcriptomes from five human B cell subsets, including a newly defined effector B cell subset, from subjects with SLE and healthy controls. Our data define a differentiation hierarchy for the subsets and elucidate the epigenetic and transcriptional differences between effector and memory B cells. Importantly, an SLE molecular signature was already established in resting naive cells and was dominated by enrichment of accessible chromatin in motifs for AP-1 and EGR transcription factors. Together, these factors acted in synergy with T-BET to shape the epigenome of expanded SLE effector B cell subsets. Thus, our data define the molecular foundation of pathogenic B cell dysfunction in SLE.

DOI: 10.1038/s41590-019-0419-9

Source:https://www.nature.com/articles/s41590-019-0419-9