Metabolomics of B to Plasma Cell Differentiation
Metabolomics of B to Plasma Cell Differentiation
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DOI：
10.1021/pr200328f
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发表时间：
2011-09-01
影响因子：
4.4
通讯作者：
Sitia, Roberto
中科院分区：
文献类型：
--
作者：
Garcia-Manteiga, Jose Manuel;Mari, Silvia;Sitia, Roberto
当小B淋巴细胞在合适的信号下结合抗原时，就会激活深刻的基因蛋白质组变态，产生抗体分泌细胞。为了研究与这种分化程序相关的代谢变化，我们通过一维质子核磁共振光谱和质谱联用液相色谱法比较了分化中的小鼠B淋巴瘤细胞和原代B细胞的外泌代谢组。主成分分析，多变量统计分析，突出了顺序分化阶段的代谢标志，区分增殖和抗体分泌阶段，并揭示新的代谢途径。在增殖过程中，乳酸的产生增加，消耗必需氨基酸;大量的IG分泌被丙氨酸和谷氨酸的产生所抑制，谷氨酰胺被用作碳源和能源。值得注意的是，乙醇和5 '-甲硫基腺苷分别在蛋白质分泌的最后阶段和增殖爆发期间产生。我们的代谢组学结果与以前的基因蛋白质组学研究一致。因此，细胞外介质的代谢谱是表征分化B细胞的功能状态和鉴定新的潜在代谢途径的有用工具。
When small B lymphocytes bind antigen in the context of suitable signals, a profound geno-proteomic metamorphosis is activated that generates antibody-secreting cells. To study the metabolic changes associated with this differentiation program, we compared the exometabolome of differentiating murine B lymphoma cells and primary B cells by monodimensional proton nuclear magnetic resonance spectroscopy and mass spectrometry coupled to liquid chromatography. Principal component analysis, a multivariate statistical analysis, highlighted metabolic hallmarks of the sequential differentiation phases discriminating between the proliferation and antibody secreting phases and revealing novel metabolic pathways. During proliferation, lactate production increased together with consumption of essential amino acids; massive Ig secretion was paralleled by alanine and glutamate production, glutamine being used as carbon and energy sources. Notably, ethanol and 5'-methylthioadenosine were produced during the last phase of protein secretion and the proliferative burst, respectively. Our metabolomics results are in agreement with previous genoproteomics studies. Thus, metabolic profiling of extracellular medium is a useful tool to characterize the functional state of differentiating B cells and to identify novel underlying metabolic pathways.