美国匹兹堡大学Mark J. Shlomchik和Florian J. Weisel研究团队发现生生殖中心B细胞（GCBC）选择性地氧化脂肪酸（FAs）以获取能量，同时进行最少程度的糖酵解。2020年2月17日，《自然—免疫学》在线发表了这一成果。
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。他们报道GCBCs在增殖的B和T细胞中是例外，因为它们能主动氧化FAs并进行最小程度的糖酵解。在体外，GCBCs的糖酵解细胞外酸化率非常低，但是响应FAs消耗氧气。[13C6]-葡萄糖饲喂表明，GCBC产生明显较少的磷酸化葡萄糖以及少量乳酸。
此外，GCBC不会将葡萄糖代谢为三羧酸（TCA）循环中间体。相反，[13C16]-棕榈酸标记表明GCBC代谢FA生成大部分的乙酰辅酶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会导致GCBC的选择性还原。因此，GCBCs似乎使有氧糖酵解和快速增殖解耦联。
据介绍，GCBC对于产生长寿命的体液免疫至关重要。人们对GCBCs如何应对快速增殖这一充满活力的挑战知之甚少。
附：英文原文
Title: Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis
Author: Florian J. Weisel, Steven J. Mullett, Rebecca A. Elsner, Ashley V. Menk, Nikita Trivedi, Wei Luo, Daniel Wikenheiser, William F. Hawse, Maria Chikina, Shuchi Smita, Laura J. Conter, Stephen M. Joachim, Stacy G. Wendell, Michael J. Jurczak, Thomas H. Winkler, Greg M. Delgoffe, Mark J. Shlomchik
Issue&Volume: 2020-02-17
Abstract: 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.
DOI: 10.1038/s41590-020-0598-4
Source: https://www.nature.com/articles/s41590-020-0598-4
Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex
本期文章：《自然—免疫学》：Online/在线发表
