UMR1227, LBAI, INSERM, Univ Brest, Brest, France.
UMR U1236, INSERM, Etablissement Français du Sang (EFS) de Bretagne, Université de Rennes 1, Rennes, France.
Immunology. 2021 Sep;164(1):120-134. doi: 10.1111/imm.13344. Epub 2021 May 26.
Antibody-secreting cells (ASC) are divided into two principal subsets, including the long-lived plasma cell (PC) subset residing in the bone marrow and the short-lived subset, also called plasmablast (PB). PB are described as a proliferating subset circulating through the blood and ending its differentiation in tissues. Due to their inherent heterogeneity, the molecular signature of PB is not fully established. The purpose of this study was to decipher a specific PB signature in humans and mice through a comprehensive meta-analysis of different data sets exploring the PB differentiation in both species and across different experimental conditions. The present study used recent analyses using whole RNA sequencing in prdm1-GFP transgenic mice to define a reliable and accurate PB signature. Next, we performed similar analysis using current data sets obtained from human PB and PC. The PB-specific signature is composed of 155 and 113 genes in mouse and human being, respectively. Although only nine genes are shared between the human and mice PB signature, the loss of B-cell identity such as the down-regulation of PAX5, MS4A1, (CD20) CD22 and IL-4R is a conserved feature across species and across the different experimental conditions. Additionally, we observed that the IRF8 and IRF4 transcription factors have a specific dynamic range of expression in human PB. We thus demonstrated that IRF4/IRF8 intranuclear staining was useful to define PB in vivo and in vitro and able to discriminate between atypical PB populations and transient states.
抗体分泌细胞（ASC）可分为两个主要亚群，包括存在于骨髓中的长寿浆细胞（PC）亚群和短暂存在的浆母细胞（PB）亚群。PB 被描述为增殖亚群，循环于血液中，并在组织中结束其分化。由于其固有异质性，PB 的分子特征尚未完全确定。本研究旨在通过对不同数据集的全面荟萃分析，解码人类和小鼠中特定的 PB 特征，这些数据集探索了两种物种以及不同实验条件下 PB 的分化。本研究使用最近在 prdm1-GFP 转基因小鼠中进行的全 RNA 测序分析来定义可靠和准确的 PB 特征。接下来，我们使用从人类 PB 和 PC 获得的当前数据集进行类似的分析。PB 特异性特征在小鼠和人类中分别由 155 和 113 个基因组成。尽管人类和小鼠 PB 特征之间仅共享九个基因，但 B 细胞特征的丧失，如 PAX5、MS4A1、（CD20）CD22 和 IL-4R 的下调，是跨物种和不同实验条件的保守特征。此外，我们观察到 IRF8 和 IRF4 转录因子在人类 PB 中有特定的表达动态范围。因此，我们证明了 IRF4/IRF8 核内染色可用于体内和体外定义 PB，并能够区分异常 PB 群体和短暂状态。
