Arginine deficiency affects early B cell maturation and lymphoid organ development in transgenic mice
Arginine deficiency affects early B cell maturation and lymphoid organ development in transgenic mice
复制标题
DOI：
10.1172/jci0216143
复制
发表时间：
2002-11-01
影响因子：
15.9
通讯作者：
Lamers, WH
中科院分区：
文献类型：
--
作者：
de Jonge, WJ;Kwikkers, KL;Lamers, WH
除了它在蛋白质和一氧化氮（NO）的合成中的作用，以及在氨解毒中，氨基酸精氨酸发挥免疫支持功能。我们研究了精氨酸在出生后免疫系统发育中的免疫防御机制中的作用。在乳鼠中，精氨酸在小肠中产生。在肠细胞中过表达精氨酸酶的F/A-2（+/+）转基因小鼠中，循环和组织精氨酸浓度降低至对照组的30-35%。在这些小鼠中，T细胞区室的发育和组成没有显示异常。然而，在外周淋巴器官和小肠中，B细胞结构和派尔集合淋巴结的数量和大小急剧减少，血清IgM水平显著降低。这些表型可以追溯到骨髓中从原B细胞阶段到前B细胞阶段的受损过渡。骨髓中的细胞因子受体水平正常。少数外周B细胞的发育和体外刺激后的增殖反应正常。B细胞成熟的障碍依赖于精氨酸水平的降低，因为这种表型在精氨酸补充后消失，并且在NO合酶或鸟氨酸转氨甲酰酶缺陷小鼠中未观察到。我们的结论是精氨酸缺乏损害早期B细胞成熟。
Apart from its role in the synthesis of protein and nitric oxide (NO), and in ammonia detoxification, the amino acid arginine exerts an immunosupportive function. We have studied the role of arginine in immune defense mechanisms in the developing postnatal immune system. In suckling mice, arginine is produced in the small intestine, In F/A-2(+/+) transgenic mice, which overexpress arginase in their enterocytes, circulating and tissue arginine concentrations are reduced to 30-35% of controls. In these mice, the development and composition of the T cell compartment did not reveal abnormalities. However, in peripheral lymphoid organs and the small intestine, B cell cellularity and the number and size of Peyer's patches were drastically reduced, and serum IgM levels were significantly decreased. These phenotypes could be traced to an impaired transition from the pro- to pre-B cell stage in the bone marrow. Cytokine receptor levels in the bone marrow were normal. The development of the few peripheral B cells and their proliferative response after in vitro stimulation was normal. The disturbance in B cell maturation was dependent on decreased arginine levels, as this phenotype disappeared upon arginine supplementation and was not seen in NO synthase- or ornithine transcarbamoylase-deficient mice. We conclude that arginine deficiency impairs early B cell maturation.