BFL-1 is an understudied anti-apoptotic protein upregulated in cancer and Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines (LCLs). We have previously shown that BFL23 1 is regulated through viral EBNA3A-mediated alterations in B-cell chromatin conformation (Price et al., 2017). Here, we extend those findings to define cis- and trans-acting factors that regulate BFL-1 in LCLs and reliance on BFL-1 for survival from extrinsic apoptosis. Beyond LCLs, BFL-1 is expressed in B cells maturing in the germinal center (GC). We therefore characterized the gene expression profiles and chromatin landscape of maturing human tonsillar B-cell subsets. While chromatin accessibility at the BFL-1 locus increases as naïve B cells enter the GC reaction, BFL29 1 expression increases during the transition from dark zone to light zone (LZ) correlating with association between enhancer regions and the transcriptional start site. The relationship between LCLs and LZ B cells suggests that EBV phenocopies GC biology to enhance their survival in establishing latent infection.

中文翻译：

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爱泼斯坦-巴尔病毒通过生发中心光区染色质结构促进存活

BFL-1是一种在癌症和Epstein-Barr病毒（EBV）永生化的淋巴母细胞样细胞系（LCL）中上调的，尚未充分研究的抗凋亡蛋白。我们之前已经证明BFL23 1是通过病毒EBNA3A介导的B细胞染色质构象变化来调节的（Price等，2017）。在这里，我们扩展了这些发现，以定义在LCL中调节BFL-1的顺式和反式作用因子，并依赖BFL-1来从外源性凋亡中存活。除了LCL外，BFL-1在发芽中心（GC）中成熟的B细胞中表达。因此，我们表征了成熟的扁桃体B细胞亚群的基因表达谱和染色质分布。随着幼稚B细胞进入GC反应，BFL-1位点的染色质可及性增加，BFL29 1表达在从暗区到亮区（LZ）的过渡过程中增加，与增强子区域和转录起始位点之间的关联相关。LCL和LZ B细胞之间的关系表明EBV表型复制GC生物学以增强其在建立潜在感染中的存活率。