Table_6_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细胞的分化在基因组学和转录组学层面已被广泛研究；然而，迄今为止，尚无研究能够从蛋白质组学的角度对依赖于抗原成熟的B细胞群体进行详细分析。本研究首次利用无标记的液相色谱-质谱-质谱（LC-MS/MS）方法，对来自人类扁桃体的5种纯化的B细胞亚群（原始B细胞、生发中心B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获取，标识符为PXD006191）。研究结果揭示了这些B细胞亚群之间的实际差异是由每个B细胞亚群内成熟阶段特异性蛋白的表达以及与代谢调节相关的相对蛋白质表达水平的变化所共同构成的，这些变化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细胞成熟阶段的转换过程中，调节与代谢调节和编程相关的分子比值的调控在诸多信号级联反应（如抗原识别和呈递及细胞存活）中的关键作用。