Department of Systems Biology, City of Hope Comprehensive Cancer Center, Monrovia, CA, USA.
Nat Rev Immunol. 2019 May;19(5):337-348. doi: 10.1038/s41577-019-0154-3.
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.
B 细胞在葡萄糖和能量代谢方面面临多种限制。其谱系决定转录因子抑制葡萄糖摄取和戊糖磷酸途径活性，而它们数量较少的线粒体和较小的细胞质体积限制了线粒体 ATP 产生和自噬作为替代能源的能力。在激活过程中，B 细胞可以平衡能量消耗的暂时增加。然而，激酶的永久过度激活，例如，自身反应性 B 细胞受体（BCR）或转化致癌基因下游的激酶的过度激活，会导致能量应激和细胞死亡。在这里，我提出 B 细胞内在的 ATP 限制代表了消除自身反应性或恶性前 B 细胞的一种保障机制。如果代谢的守门员受到损害，额外葡萄糖的流入可能会为自身反应性 BCR 或转化致癌基因驱动的病理性 B 细胞增殖和永久增加的代谢需求提供燃料。
