Table_7_Dynamic Intracellular Metabolic Cell Signaling Profiles During Ag-Dependent B-Cell Differentiation.xlsx

Human B-cell differentiation has been extensively investigated on genomic and transcriptomic grounds; however, no studies have accomplished so far detailed analysis of antigen-dependent maturation-associated human B-cell populations from a proteomic perspective. Here, we investigate for the first time the quantitative proteomic profiles of B-cells undergoing antigen-dependent maturation using a label-free LC-MS/MS approach applied on 5 purified B-cell subpopulations (naive, centroblasts, centrocytes, memory and plasma B-cells) from human tonsils (data are available via ProteomeXchange with identifier PXD006191). Our results revealed that the actual differences among these B-cell subpopulations are a combination of expression of a few maturation stage-specific proteins within each B-cell subset and maturation-associated changes in relative protein expression levels, which are related with metabolic regulation. The considerable overlap of the proteome of the 5 studied B-cell subsets strengthens the key role of the regulation of the stoichiometry of molecules associated with metabolic regulation and programming, among other signaling cascades (such as antigen recognition and presentation and cell survival) crucial for the transition between each B-cell maturation stage.

人类B细胞分化的基因组学和转录组学研究已得到广泛开展；然而，迄今为止，尚未有研究从蛋白质组学角度对抗原依赖性成熟相关的人类B细胞群体进行详细分析。本研究首次采用无标记液相色谱-串联质谱（LC-MS/MS）技术，对从人类扁桃体中提取的5种纯化的B细胞亚群（包括初始B细胞、中心母细胞、中心细胞、记忆B细胞和浆细胞）进行定量蛋白质组学研究（数据可通过ProteomeXchange平台，使用标识符PXD006191获取）。研究发现，这些B细胞亚群之间的实际差异是由每个B细胞亚群中少量成熟阶段特异性蛋白的表达以及与代谢调节相关的蛋白质表达水平的变化所共同决定的，后者与代谢调节密切相关。所研究的5种B细胞亚群的蛋白质组存在显著的重叠，这进一步强调了在B细胞成熟各阶段之间的过渡中，调节与代谢调节和程序化相关的分子 stoichiometry 的关键作用，以及其他信号级联（如抗原识别和呈递以及细胞存活）的重要性。