Center for Neuroinflammation and Experimental Therapeutics, and.
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
JCI Insight. 2023 Apr 10;8(7):e155199. doi: 10.1172/jci.insight.155199.
B cells within secondary lymphoid tissues encompass a diversity of activation states and multiple maturation processes that reflect antigen recognition and transition through the germinal center (GC) reaction, in which mature B cells differentiate into memory and antibody-secreting cells (ASCs). Here, utilizing single-cell RNA-seq, we identify a range of distinct activation and maturation states of tonsil-derived B cells. In particular, we identify what we believe is a previously uncharacterized CCL4/CCL3 chemokine-expressing B cell population with an expression pattern consistent with B cell receptor/CD40 activation. Furthermore, we present a computational method that leverages regulatory network inference and pseudotemporal modeling to identify upstream transcription factor modulation along a GC-to-ASC axis of transcriptional maturation. Our data set provides valuable insight into diverse B cell functional profiles and will be a useful resource for further studies into the B cell immune compartment.
次级淋巴组织中的 B 细胞包含多种激活状态和多个成熟过程,这些过程反映了抗原的识别以及通过生发中心(GC)反应的转变,在此过程中,成熟 B 细胞分化为记忆 B 细胞和分泌抗体的细胞(ASCs)。在这里,我们利用单细胞 RNA 测序技术,鉴定了扁桃体来源的 B 细胞的一系列不同的激活和成熟状态。特别是,我们鉴定出了一种我们认为是以前未被描述的 CCL4/CCL3 趋化因子表达的 B 细胞群体,其表达模式与 B 细胞受体/CD40 的激活一致。此外,我们提出了一种计算方法,该方法利用调控网络推断和拟时建模来鉴定沿着 GC-ASC 转录成熟轴的上游转录因子的调节。我们的数据集提供了对不同 B 细胞功能谱的有价值的见解,并且将成为进一步研究 B 细胞免疫区室的有用资源。