Functionally significant metabolic differences between B and T lymphocyte lineages

Functionally significant metabolic differences between B and T lymphocyte lineages
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DOI:
10.1111/imm.13098
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发表时间:
2019-08-26
期刊:
影响因子:
6.4
通讯作者:
Arimbasseri, Gopalakrishnan Aneeshkumar
Arimbasseri, Gopalakrishnan Aneeshkumar
中科院分区:
医学2区
文献类型:
--
作者:
Khalsa, Jasneet Kaur;Chawla, Amanpreet Singh;Arimbasseri, Gopalakrishnan Aneeshkumar

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B淋巴细胞和T淋巴细胞的激活导致细胞代谢景观的重大重塑,使其激活后的功能成为可能。然而,幼稚B淋巴细胞和T淋巴细胞也表现出代谢差异,这些差异的发生、性质和功能意义尚不清楚。在这里,我们发现休眠的b细胞似乎比休眠的t细胞有更低的能量需求,因为它们消耗更低水平的葡萄糖和脂肪酸,产生更少的ATP。静止的b细胞更依赖于OXPHOS,而t细胞更依赖于有氧糖酵解。然而,尽管能量需求明显更高,但T系细胞的蛋白质合成率低于B系细胞。这两个谱系之间的代谢差异是在谱系分化的早期建立的,并且在功能上是显著的。b细胞中较高水平的蛋白质合成与MHC II类分子和其他与抗原内化、运输和呈递相关的蛋白质合成增加有关。t细胞中较高的能量需求和较低的蛋白质合成的结合与它们较高的atp依赖性运动性是一致的。我们的数据提供了B和T淋巴细胞谱系之间代谢差异及其功能含义的综合视角。
Activation of B and T lymphocytes leads to major remodelling of the metabolic landscape of the cells enabling their post-activation functions. However, naive B and T lymphocytes also show metabolic differences, and the genesis, nature and functional significance of these differences are not yet well understood. Here we show that resting B-cells appeared to have lower energy demands than resting T-cells as they consumed lower levels of glucose and fatty acids and produced less ATP. Resting B-cells are more dependent on OXPHOS, while T-cells show more dependence on aerobic glycolysis. However, despite an apparently higher energy demand, T lineage cells showed lower rates of protein synthesis than equivalent B lineage stages. These metabolic differences between the two lineages were established early during lineage differentiation, and were functionally significant. Higher levels of protein synthesis in B-cells were associated with increased synthesis of MHC class II molecules and other proteins associated with antigen internalization, transport and presentation. The combination of higher energy demand and lower protein synthesis in T-cells was consistent with their higher ATP-dependent motility. Our data provide an integrated perspective of the metabolic differences and their functional implications between the B and T lymphocyte lineages.