免疫系统
生物
自身免疫
获得性免疫系统
转录因子
遗传学
转录组
周边公差
表观遗传学
计算生物学
免疫学
表观遗传学
表观基因组
DNA甲基化
B细胞
基因
生发中心
染色质
基因表达
抗体
作者
Hamish W. King,Kristen L. Wells,Zohar Shipony,Arwa S. Kathiria,Lisa E. Wagar,Caleb A. Lareau,Nara Orban,Robson Capasso,Mark M. Davis,Lars M. Steinmetz,Louisa K. James,William J. Greenleaf
标识
DOI:10.1101/2021.03.16.435578
摘要
Abstract The germinal center (GC) response is critical for both effective adaptive immunity and establishing peripheral tolerance by limiting auto-reactive B cells. Dysfunction in these processes can lead to defects in immune response to pathogens or contribute to autoimmune disease. To understand the gene regulatory principles underlying the GC response, we generated a single-cell transcriptomic and epigenomic atlas of the human tonsil, a widely studied and representative lymphoid tissue. We characterize diverse immune cell subsets and build a trajectory of dynamic gene expression and transcription factor activity during B cell activation, GC formation, and plasma cell differentiation. We subsequently leverage cell type-specific transcriptomic and epigenomic maps to interpret potential regulatory impact of genetic variants implicated in autoimmunity, revealing that many exhibit their greatest regulatory potential in GC cell populations. Together, these analyses provide a powerful new cell type-resolved resource for the interpretation of cellular and genetic causes underpinning autoimmune disease. One sentence summary Single-cell chromatin accessibility landscapes of immune cell subsets reveal regulatory potential of autoimmune-associated genetic variants during the germinal center response.
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