Table_5_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细胞分化的基因组及转录组研究已得到广泛开展；然而，迄今为止，尚无研究能够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-质谱联用技术，对来自人类扁桃体的5个纯化的B细胞亚群（包括原始B细胞、中心细胞、中心母细胞、记忆B细胞和浆细胞）进行定量蛋白质组学分析（数据可通过ProteomeXchange平台，使用标识符PXD006191获取）。我们的研究结果表明，这些B细胞亚群之间的实际差异是由每个B细胞亚群中成熟阶段特异性蛋白质的表达以及相对蛋白质表达水平与代谢调节相关的成熟相关变化共同构成。五个研究B细胞亚群的蛋白质组之间显著的相似性强化了在信号级联反应（如抗原识别与呈递及细胞存活等对B细胞成熟阶段过渡至关重要的过程）中，调节与代谢调节和程序化相关的分子计量比在调控机制中的核心作用。