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Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis
Nature Immunology ( IF 30.5 ) Pub Date : 2020-02-17 , DOI: 10.1038/s41590-020-0598-4
Florian J Weisel 1 , Steven J Mullett 2 , Rebecca A Elsner 1 , Ashley V Menk 3 , Nikita Trivedi 1 , Wei Luo 1 , Daniel Wikenheiser 1 , William F Hawse 1 , Maria Chikina 4 , Shuchi Smita 1, 4 , Laura J Conter 1 , Stephen M Joachim 1 , Stacy G Wendell 2, 5 , Michael J Jurczak 6, 7 , Thomas H Winkler 8 , Greg M Delgoffe 1, 3 , Mark J Shlomchik 1
Affiliation  

Germinal center B cells (GCBCs) are critical for generating long-lived humoral immunity. How GCBCs meet the energetic challenge of rapid proliferation is poorly understood. Dividing lymphocytes typically rely on aerobic glycolysis over oxidative phosphorylation for energy. Here we report that GCBCs are exceptional among proliferating B and T cells, as they actively oxidize fatty acids (FAs) and conduct minimal glycolysis. In vitro, GCBCs had a very low glycolytic extracellular acidification rate but consumed oxygen in response to FAs. [13C6]-glucose feeding revealed that GCBCs generate significantly less phosphorylated glucose and little lactate. Further, GCBCs did not metabolize glucose into tricarboxylic acid (TCA) cycle intermediates. Conversely, [13C16]-palmitic acid labeling demonstrated that GCBCs generate most of their acetyl-CoA and acetylcarnitine from FAs. FA oxidation was functionally important, as drug-mediated and genetic dampening of FA oxidation resulted in a selective reduction of GCBCs. Hence, GCBCs appear to uncouple rapid proliferation from aerobic glycolysis.



中文翻译:

生发中心 B 细胞选择性地氧化脂肪酸获取能量,同时进行最小的糖酵解

生发中心 B 细胞 (GCBC) 对于产生长寿命的体液免疫至关重要。GCBC 如何应对快速增殖的能量挑战尚不清楚。分裂的淋巴细胞通常依靠有氧糖酵解而不是氧化磷酸化来获取能量。在这里,我们报告 GCBC 在增殖的 B 细胞和 T 细胞中是特殊的,因为它们积极氧化脂肪酸 (FA) 并进行最小的糖酵解。在体外,GCBCs 具有非常低的糖酵解细胞外酸化率,但响应 FAs 会消耗氧气。[ 13 C 6 ]-葡萄糖喂养表明,GCBCs 产生的磷酸化葡萄糖和乳酸含量显着减少。此外,GCBC 不会将葡萄糖代谢成三羧酸 (TCA) 循环中间体。相反, [ 13 C16 ]-棕榈酸标记表明GCBCs从FAs中产生大部分乙酰辅酶A和乙酰肉碱。FA 氧化在功能上很重要,因为 FA 氧化的药物介导和遗传抑制导致 GCBC 的选择性减少。因此,GCBC 似乎将快速增殖与有氧糖酵解脱钩。

更新日期:2020-02-17
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