Effects of in utero alcohol exposure on B-cell development in the murine fetal liver
Effects of in utero alcohol exposure on B-cell development in the murine fetal liver
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DOI：
10.1111/j.1530-0277.1998.tb03969.x
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发表时间：
1998-11-01
影响因子：
3.2
通讯作者：
Wolcott, RM
中科院分区：
文献类型：
--
作者：
Biber, KL;Moscatello, KM;Wolcott, RM
胎儿酒精综合征是导致出生缺陷的主要原因之一。在子宫内接触酒精的儿童会遭受生长和智力迟钝、身体畸形和免疫功能障碍。这个实验室以前的工作表明，在子宫内接触酒精的小鼠的B淋巴细胞生成延迟。B细胞发育的缺陷在出生后不久就很明显，并延长到断奶后。由于淋巴细胞生成始于胎儿肝脏，因此目前的研究旨在确定胎儿B细胞发育是否也受到子宫内酒精暴露的影响。我们现在表明，子宫内酒精暴露对B淋巴细胞生成的影响直到妊娠后期才变得明显。流式细胞术用于计数a细胞发育途径中的几个中间体。这些表型分析表明，在妊娠第17天之前，与对照动物相比，B系中间体发育正常。然而，在妊娠第17和18天之间，B系中间体的群体动力学异常在暴露于酒精的小鼠的胎儿肝脏中变得明显。B细胞发育途径中的早期中间体以正常数量存在;然而，到妊娠第18天，更成熟的祖细胞以及B细胞的数量减少。这些数据表明，子宫内酒精暴露破坏了B系中间体沿着发育途径发展至成熟的能力，从而使动物在出生时免疫功能低下。
Fetal alcohol syndrome is one of the leading causes of birth defects in this country. Children exposed to alcohol in utero suffer from growth and mental retardation, physical abnormalities, and immune dysfunction. Previous work from this laboratory demonstrated that B lymphopoiesis Is delayed in mice exposed to alcohol in utero. The deficit in B-cell development was apparent shortly after birth and extended to well after weaning. Because lymphopoiesis begins in the fetal liver, the current study was done to determine if fetal B-cell development was effected as well by in utero exposure to alcohol. We now show that the effects of in utero alcohol exposure on B lymphopoiesis do not become apparent until later in gestation, Flow cytometry was used to enumerate several intermediates in the a-cell developmental pathway. These phenotypic analyses showed that before day 17 of gestation, B-lineage intermediates developed normally when compared with control animals. However, between days 17 and 18 of gestation, an abnormality in the population dynamics of B-lineage intermediates became apparent in the fetal fiver of alcohol-exposed mice. Early intermediates in the B-cell developmental pathway wets present in normal numbers; however, the more mature progenitors as well as B cells were decreased in number by gestational day 18, These data suggest that in utero alcohol exposure disrupts the ability of B-lineage intermediates to progress along the developmental pathway to maturity, thereby leaving the animal immunocompromised at birth.