Proteome profiling suggests a pro‐inflammatory role for plasma cells through release of high‐mobility group box 1 protein

Proteome profiling suggests a pro‐inflammatory role for plasma cells through release of high‐mobility group box 1 protein
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蛋白质组分析表明浆细胞通过释放高迁移率 Group Box 1 蛋白发挥促炎作用

DOI:
10.1002/pmic.201000491
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发表时间:
2011
期刊:
影响因子:
3.4
通讯作者:
Jäck H-M
Jäck H-M
中科院分区:
生物学3区
文献类型:
--
作者:
Vettermann;Castor D;Mekker A;Gerrits B;Karas M;Jäck H-M

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B-细胞成熟的最后一步是分化成浆细胞,这一过程伴随着亚细胞组织的总体变化,以使抗体分泌。为了更好地理解建立体液免疫应答的这一关键步骤,我们结合2-DE/MS分析了浆细胞分化过程中的蛋白质组动力学。当脂多糖(LPS)刺激的原代B细胞分化为分泌抗体的浆细胞时,32个鉴定的蛋白质点的相对丰度发生了变化。蛋白质和转录本丰度的相关分析表明,这些蛋白质中有三分之一是转录后调节的。除了ER驻留分子伴侣,脂质代谢酶和翻译起始因子外,我们还鉴定了几种以前未在浆细胞中研究过的蛋白质。其中之一是瞬时上调的蛋白酶体激活剂(PA)28γ,一种推定的核蛋白酶体的组分。此外,我们发现非典型炎性细胞因子高迁移率族蛋白1(HMG 1)从浆细胞释放到细胞外环境中。这表明浆细胞作为促炎介质的新作用,这对各种自身免疫性疾病和慢性炎症具有重要意义。
The final step of B‐cell maturation is to differentiate into plasma cells, a process that is accompanied by gross changes in subcellular organization to enable antibody secretion. To better understand this critical step in mounting a humoral immune response, we analyzed proteome dynamics during plasma cell differentiation with combined 2‐DE/MS. Thirty‐two identified protein spots changed in relative abundance when lipopolysaccharide (LPS)‐stimulated primary B cells differentiated into antibody‐secreting plasma cells. A correlative analysis of protein and transcript abundance suggested that one third of these proteins are post‐transcriptionally regulated. Apart from ER‐resident chaperones, lipid metabolic enzymes, and translation initiation factors, we identified several proteins that had not been previously studied in plasma cells. Among them is the transiently upregulated proteasome activator (PA) 28γ, a component of the putative nuclear proteasome. Additionally, we discovered that the non‐canonical inflammatory cytokine high‐mobility group box 1 (HMG1) was released from plasma cells into the extracellular milieu. This suggests a novel role for plasma cells as pro‐inflammatory mediators, which has important implications for various autoimmune diseases and chronic inflammation.
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