Institute of Biomedical Technology, University of Tampere, Tampere, Finland ; BioMediTech, Tampere, Finland ; Research Unit, Tampere University Hospital, Tampere, Finland.
PLoS One. 2013 Oct 29;8(10):e77894. doi: 10.1371/journal.pone.0077894. eCollection 2013.
B cells play a pivotal role in adaptive immune system, since they maintain a delicate balance between recognition and clearance of foreign pathogens and tolerance to self. During maturation, B cells progress through a series of developmental stages defined by specific phenotypic surface markers and the rearrangement and expression of immunoglobulin (Ig) genes. To get insight into B cell proteome during the maturation pathway, we studied differential protein expression in eight human cell lines, which cover four distinctive developmental stages; early pre-B, pre-B, plasma cell and immature B cell upon anti-IgM stimulation. Our two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry based proteomic study indicates the involvement of large number of proteins with various functions. Notably, proteins related to cytoskeleton were relatively highly expressed in early pre-B and pre-B cells, whereas plasma cell proteome contained endoplasmic reticulum and Golgi system proteins. Our long time series analysis in anti-IgM stimulated Ramos B cells revealed the dynamic regulation of cytoskeleton organization, gene expression and metabolic pathways, among others. The findings are related to cellular processes in B cells and are discussed in relation to experimental information for the proteins and pathways they are involved in. Representative 2D-DIGE maps of different B cell maturation stages are available online at http://structure.bmc.lu.se/BcellProteome/.
B 细胞在适应性免疫系统中起着至关重要的作用,因为它们在识别和清除外来病原体与自身耐受之间保持着微妙的平衡。在成熟过程中,B 细胞经历了一系列发育阶段,这些阶段由特定的表型表面标志物以及免疫球蛋白(Ig)基因的重排和表达来定义。为了深入了解 B 细胞在成熟途径中的蛋白质组,我们研究了八种人类细胞系中差异表达的蛋白质,这些细胞系涵盖了四个不同的发育阶段:抗 IgM 刺激后的早期前 B、前 B、浆细胞和未成熟 B 细胞。我们的二维差异凝胶电泳(2D-DIGE)和基于质谱的蛋白质组学研究表明,大量具有不同功能的蛋白质参与其中。值得注意的是,与细胞骨架相关的蛋白质在前 B 和前 B 细胞中相对高度表达,而浆细胞的蛋白质组包含内质网和高尔基体系统的蛋白质。我们对抗 IgM 刺激的 Ramos B 细胞进行的长时间序列分析揭示了细胞骨架组织、基因表达和代谢途径等的动态调节。这些发现与 B 细胞中的细胞过程有关,并结合了它们所涉及的蛋白质和途径的实验信息进行了讨论。不同 B 细胞成熟阶段的代表性 2D-DIGE 图谱可在 http://structure.bmc.lu.se/BcellProteome/ 上在线获取。