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Metabolic gatekeepers to safeguard against autoimmunity and oncogenic B cell transformation.
Nature Reviews Immunology ( IF 67.7 ) Pub Date : 2019-05-01 , DOI: 10.1038/s41577-019-0154-3 Markus Müschen 1
Nature Reviews Immunology ( IF 67.7 ) Pub Date : 2019-05-01 , DOI: 10.1038/s41577-019-0154-3 Markus Müschen 1
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B cells face multiple restrictions on glucose and energy metabolism. Their lineage-determining transcription factors repress glucose uptake and pentose phosphate pathway activity, while their low numbers of mitochondria and small cytoplasmic volume set narrow limits for mitochondrial ATP production and autophagy as alternative energy sources. During activation, B cells can balance temporary increases of energy expenditure. However, permanent hyperactivation of kinases, for instance, downstream of an autoreactive B cell receptor (BCR) or a transforming oncogene, can cause energy stress and cell death. Here, I propose that B cell-intrinsic restriction of ATP represents a safeguard to eliminate autoreactive or pre-malignant B cells. If the metabolic gatekeepers are compromised, influx of additional glucose may fuel permanent increases in metabolic demands and pathological B cell proliferation, driven by an autoreactive BCR or a transforming oncogene.
中文翻译：
代谢把关者可预防自身免疫和致癌B细胞转化。
B细胞在葡萄糖和能量代谢方面面临多重限制。它们的谱系决定转录因子抑制葡萄糖的摄取和戊糖磷酸途径的活性，而线粒体的数量少和细胞质的体积小，将线粒体ATP的产生和自噬作为替代能源设定了狭窄的界限。在激活期间，B电池可以平衡能量消耗的暂时增加。但是，激酶的永久过度活化，例如自身反应性B细胞受体（BCR）或转化癌基因的下游，可能导致能量紧张和细胞死亡。在这里，我建议对ATP的B细胞本征限制是消除自身反应性或恶性前B细胞的一种保障措施。如果新陈代谢的守门员受到损害，
更新日期：2019-05-16
中文翻译：
代谢把关者可预防自身免疫和致癌B细胞转化。
B细胞在葡萄糖和能量代谢方面面临多重限制。它们的谱系决定转录因子抑制葡萄糖的摄取和戊糖磷酸途径的活性，而线粒体的数量少和细胞质的体积小，将线粒体ATP的产生和自噬作为替代能源设定了狭窄的界限。在激活期间，B电池可以平衡能量消耗的暂时增加。但是，激酶的永久过度活化，例如自身反应性B细胞受体（BCR）或转化癌基因的下游，可能导致能量紧张和细胞死亡。在这里，我建议对ATP的B细胞本征限制是消除自身反应性或恶性前B细胞的一种保障措施。如果新陈代谢的守门员受到损害，
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