B1a B cells require autophagy for metabolic homeostasis and self-renewal.
B1a B cells require autophagy for metabolic homeostasis and self-renewal.
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DOI：
10.1084/jem.20170771
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发表时间：
2018-02-05
期刊：
影响因子：
--
通讯作者：
Simon AK
中科院分区：
文献类型：
--
作者：
Clarke AJ;Riffelmacher T;Braas D;Cornall RJ;Simon AK
Clarke等人证明，先天样B1 B细胞亚群具有独特的代谢表型，其特征在于高水平的糖酵解、戊糖磷酸途径和TCA循环活性，并且依赖于自噬以实现代谢稳态和自我更新。特定的代谢程序被免疫细胞激活，以履行其功能作用，包括适应其微环境。B1 B细胞是组织驻留的先天性B细胞。它们具有许多独特的特性，例如自我更新的能力和对有限的表位库快速响应的能力。支持这些功能的代谢途径尚不清楚。我们发现B1 B细胞比B2 B细胞在生物能量上更活跃，具有更高的糖酵解和氧化磷酸化速率，并且依赖于糖酵解。它们获取外源性脂肪酸并以液滴形式储存脂质。自噬在B1a B细胞中被差异激活，自噬基因Atg 7的缺失导致由自我更新失败引起的B1a B细胞的选择性丧失。自噬缺陷的B1 a B细胞下调关键代谢基因并积累功能失调的线粒体。因此，B1 B细胞已经进化出适应其驻留和特定功能特性的独特代谢。
Clarke et al. demonstrate that the innate-like B1 B cell subset has a distinct metabolic phenotype, characterized by high levels of glycolysis, pentose phosphate pathway, and TCA cycle activity, and depends on autophagy for metabolic homeostasis and self-renewal. Specific metabolic programs are activated by immune cells to fulfill their functional roles, which include adaptations to their microenvironment. B1 B cells are tissue-resident, innate-like B cells. They have many distinct properties, such as the capacity to self-renew and the ability to rapidly respond to a limited repertoire of epitopes. The metabolic pathways that support these functions are unknown. We show that B1 B cells are bioenergetically more active than B2 B cells, with higher rates of glycolysis and oxidative phosphorylation, and depend on glycolysis. They acquire exogenous fatty acids and store lipids in droplet form. Autophagy is differentially activated in B1a B cells, and deletion of the autophagy gene Atg7 leads to a selective loss of B1a B cells caused by a failure of self-renewal. Autophagy-deficient B1a B cells down-regulate critical metabolic genes and accumulate dysfunctional mitochondria. B1 B cells, therefore, have evolved a distinct metabolism adapted to their residence and specific functional properties.
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