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Conserved epigenetic programming and enhanced heme metabolism drive memory B cell reactivation
bioRxiv - Immunology Pub Date : 2021-01-21 , DOI: 10.1101/2021.01.20.427446
Madeline J. Price , Christopher D. Scharer , Anna K. Kania , Troy D. Randall , Jeremy M. Boss

Memory B cells (MBCs) have enhanced capabilities to differentiate to plasma cells and generate a rapid burst of antibodies upon secondary stimulation. To determine if MBCs harbor an epigenetic landscape that contributes to increased differentiation potential, we derived the chromatin accessibility and transcriptomes of influenza-specific IgM and IgG MBCs compared to naive cells. MBCs possessed an accessible chromatin architecture surrounding plasma cell specific genes, as well as altered expression of transcription factors and genes encoding cell cycle, chemotaxis, and signal transduction processes. Intriguingly, this MBC signature was conserved between humans and mice. MBCs of both species possessed a heightened heme signature compared to naive cells. Differentiation in the presence of hemin enhanced oxidative phosphorylation metabolism and MBC differentiation into antibody secreting plasma cells. Thus, these data define conserved MBC transcriptional and epigenetic signatures that include a central role for heme and multiple other pathways in augmenting MBC reactivation potential.

中文翻译:

保守的表观遗传程序设计和增强的血红素代谢驱动记忆B细胞活化

记忆B细胞(MBC)具有增强的能力,可以分化为浆细胞并在二次刺激后产生快速的抗体爆发。为了确定MBC是否包含有助于增加分化潜能的表观遗传景观,我们推导了与幼稚细胞相比,流感特异性IgM和IgG MBC的染色质可及性和转录组。MBC拥有围绕浆细胞特定基因的可及的染色质结构,以及转录因子和编码细胞周期,趋化性和信号转导过程的基因的表达变化。有趣的是,这种MBC标记在人和小鼠之间是保守的。与原始细胞相比,两种物种的MBC都具有更高的血红素特征。在有血红素的存在下的分化增强了氧化磷酸化代谢,并使MBC分化为分泌抗体的浆细胞。因此,这些数据定义了保守的MBC转录和表观遗传学特征,包括血红素和其他多种途径在提高MBC激活潜力方面的核心作用。
更新日期:2021-01-22
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