Transitional B cells must actively undergo selection for self-tolerance before maturing into their resting follicular B cell successors. We found that metabolic quiescence was acquired at the follicular B cell stage in both humans and mice. In follicular B cells, the expression of genes involved in ribosome biogenesis, aerobic respiration, and mammalian target of rapamycin complex 1 (mTORC1) signaling was reduced when compared to that in transitional B cells. Functional metabolism studies, profiling of whole-cell metabolites, and analysis of cell surface proteins in human B cells suggested that this transition was also associated with increased extracellular adenosine salvage. Follicular B cells increased the abundance of the cell surface ectonucleotidase CD73, which coincided with adenosine 5′-monophosphate–activated protein kinase (AMPK) activation. Differentiation to the follicular B cell stage in vitro correlated with surface acquisition of CD73 on human transitional B cells and was augmented with the AMPK agonist, AICAR. Last, individuals with gain-of-function PIK3CD (PI3Kδ) mutations and increased pS6 activation exhibited a near absence of circulating follicular B cells. Together, our data suggest that mTORC1 attenuation may be necessary for human follicular B cell development. These data identify a distinct metabolic switch during human B cell development at the transitional to follicular stages, which is characterized by an induction of extracellular adenosine salvage, AMPK activation, and the acquisition of metabolic quiescence.

过渡性B细胞在成熟成静止的滤泡性B细胞后继细胞之前必须主动进行自我耐受的选择。我们发现人类和小鼠的卵泡B细胞阶段都获得了代谢静止。在卵泡B细胞中，与过渡B细胞相比，参与核糖体生物发生，有氧呼吸和哺乳动物雷帕霉素复合物1（mTORC1）信号转导的基因的表达降低。功能代谢研究，全细胞代谢产物谱分析以及人B细胞中细胞表面蛋白的分析表明，这种转变也与细胞外腺苷拯救增加有关。滤泡性B细胞增加了细胞表面胞外核苷酸酶CD73的丰度，这与5'-单磷酸腺苷激活的蛋白激酶（AMPK）激活相吻合。体外滤泡性B细胞阶段的分化与人类过渡性B细胞上CD73的表面获取有关，并被AMPK激动剂AICAR增强。最后，有功能获得者PIK3CD（PI3Kδ）突变和增加的pS6激活表现出几乎没有循环的滤泡B细胞。在一起，我们的数据表明mTORC1衰减可能是人类卵泡B细胞发育所必需的。这些数据确定了在人类B细胞发育到卵泡期期间B细胞发育过程中独特的代谢转换，其特征是诱导胞外腺苷挽救，AMPK激活和获得代谢静止。