Metabolic requirements of human pro-inflammatory B cells in aging and obesity
Metabolic requirements of human pro-inflammatory B cells in aging and obesity
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DOI：
10.1371/journal.pone.0219545
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发表时间：
2019-07-09
期刊：
影响因子：
3.7
通讯作者：
Blomberg, Bonnie B.
中科院分区：
文献类型：
--
作者：
Frasca, Daniela;Diaz, Alain;Blomberg, Bonnie B.
促炎B细胞亚群被称为晚期记忆、组织样或双阴性(DN)，在老年人的血液中积聚。在这里，我们发现DNB细胞不增殖，也不产生针对流感抗原的抗体，但它们分泌具有自身免疫反应性的抗体，这与它们的膜表型(CD95+CD21-CD11c+)和它们自发表达的转录因子T-bet是一致的。患有肥胖症和自身免疫性疾病的人血液中的这些细胞也会增加，但相关的致病机制和信号通路只有一部分已知。在本文中，我们比较了不同年龄健康人的血液中这些细胞的频率和代谢需求，以及肥胖者的血液和皮下脂肪组织(SAT)中这些细胞的频率和代谢需求。结果表明，年轻人的糖尿病肾病B细胞的代谢需求最低，老年人和肥胖者的糖尿病肾病B细胞利用较高的葡萄糖产生自身免疫抗体，并参与有氧糖酵解以支持其功能。来自SAT的DNB细胞具有最高的代谢需求，因为它们激活了氧化磷酸化、有氧糖酵解和脂肪酸氧化。来自SAT的DNB细胞也显示出最高水平的ROS和最高水平的磷酸化AMPK(5‘-AMP激活激酶)和Sestrin 1，两者都能够缓解压力和细胞死亡。这种代谢优势推动了DNB细胞的存活和功能(自身免疫抗体的分泌)。
The subset of pro-inflammatory B cells, called late memory, tissue-like or double negative (DN), accumulates in the blood of elderly individuals. Here we show that DN B cells do not proliferate and do not make antibodies to influenza antigens, but they secrete antibodies with autoimmune reactivity, in agreement with their membrane phenotype (CD95+CD21-CD11c+) and their spontaneous expression of the transcription factor T-bet. These cells also increase in the blood of individuals with obesity and autoimmune diseases, but causative mechanisms and signaling pathways involved are known only in part. In the present paper we compare frequencies and metabolic requirements of these cells in the blood of healthy individuals of different ages and in the blood and the subcutaneous adipose tissue (SAT) of individuals with obesity. Results show that DN B cells from young individuals have minimal metabolic requirements, DN B cells from elderly and obese individuals utilize higher amounts of glucose to perform autoimmune antibody production and enroll in aerobic glycolysis to support their function. DN B cells from the SAT have the highest metabolic requirements as they activate oxidative phosphorylation, aerobic glycolysis and fatty acid oxidation. DN B cells from the SAT also show the highest levels of ROS and the highest levels of phosphorylated AMPK (5'-AMP activated kinase) and Sestrin 1, both able to mitigate stress and cell death. This metabolic advantage drives DN B cell survival and function (secretion of autoimmune antibodies).