The activated B-cell (ABC) to plasmablast transition encompasses the cusp of antibody-secreting cell (ASC) differentiation. We explore this transition with integrated analysis in human cells, focusing on changes that follow removal from CD40-mediated signals. Within hours of input signal loss, cell growth programs shift toward enhanced proliferation, accompanied by ER-stress response, and up-regulation of ASC features. Clustering of genomic occupancy for IRF4, BLIMP1, XBP1, and CTCF with histone marks identifies a dichotomy: XBP1 and IRF4 link to induced but not repressed gene modules in plasmablasts, whereas BLIMP1 links to modules of ABC genes that are repressed, but not to activated genes. Between ABC and plasmablast states, IRF4 shifts away from AP1/IRF composite elements while maintaining occupancy at IRF and ETS/IRF elements. This parallels the loss of BATF expression, which is identified as a potential BLIMP1 target. In plasmablasts, IRF4 acquires an association with CTCF, a feature maintained in plasma cell myeloma lines. Thus, shifting occupancy links IRF4 to both ABC and ASC gene expression, whereas BLIMP1 occupancy links to repression of the activation state.

中文翻译：

---

激活的 B 细胞向浆母细胞转变过程中基因调控关联的二分法。


活化的 B 细胞 (ABC) 向浆母细胞的转变包含抗体分泌细胞 (ASC) 分化的尖峰。我们通过对人体细胞的综合分析来探索这一转变，重点关注 CD40 介导的信号去除后发生的变化。输入信号丢失后数小时内，细胞生长程序转向增殖增强，并伴有 ER 应激反应和 ASC 特征上调。 IRF4、BLIMP1、XBP1 和 CTCF 的基因组占用与组蛋白标记的聚类识别出二分法：XBP1 和 IRF4 与浆母细胞中诱导但不被抑制的基因模块连接，而 BLIMP1 与被抑制但不被激活的 ABC 基因模块连接基因。在 ABC 和浆母细胞状态之间，IRF4 远离 AP1/IRF 复合元件，同时保持占据 IRF 和 ETS/IRF 元件。这与BATF表达的丧失相似，BATF 表达被确定为潜在的 BLIMP1 目标。在浆母细胞中，IRF4 与 CTCF 相关，这是浆细胞骨髓瘤系中保留的一个特征。因此，转移占据将 IRF4 与 ABC 和 ASC 基因表达联系起来，而 BLIMP1 占据与激活状态的抑制联系起来。