FETAL ALCOHOL EXPOSURE AND NEONATAL LYMPHOID DEVELOPMENT

患有胎儿酒精综合征（FAS）的婴儿通常会出现广泛的 各种免疫异常影响体液和细胞 介导的免疫系统的手臂。这个实验室最近的研究表明 子宫内暴露于乙醇会导致B细胞发育延迟 在新生小鼠中。此外，我们注意到细胞的积累，即 热稳定抗原（HsA 10和HsA 20）的低表达， 脾脏和骨骼中的泛B细胞标记物B220（B220-）阴性 暴露于乙醇的新生小鼠的骨髓。的初步鉴定 通过流式细胞术显示这种细胞类型是淋巴样的 在大小和粒度上都是一样的。HSA 10 B22 O-细胞群 占成人骨髓的10-12%，约占新生儿骨的16 骨髓。当这些细胞被分离出来，并放置在培养基质中时， 细胞和IL-7部分能分化为B220+细胞 这表明在这群细胞中存在着一个 B细胞谱系。这些祖细胞样基因的异常表达 暴露于乙醇的新生小鼠中的细胞可能揭示了 我们观察到B细胞发育延迟。这是本提案的目标 为了表征HSA 1 oB 220细胞类型，特别注意 体内和体外的发育能力。

Infants born with fetal alcohol syndrome (FAS) often present with a wide variety of immunologic anomalies affecting both the humoral and cell mediated arms of the immune system. Recent work from this lab suggests that in utero exposure to ethanol causes a delay in B cell development in neonatal mice. In addition, we noted the accumulation of a cell, that had the phenotype of low expression for heat stable antigen (HsA1o and negative for the pan B cell marker B220 (B220-), in the spleen and bone marrow of ethanol exposed neonatal mice. Preliminary characterization of this cell type by flow cytometry revealed a cell type that was 'lymphoid like' in both size and granularity. The HSA1oB22O- population of cells represented 10-12% of adult bone marrow and about 16% of neonatal bone marrow. When these cells were isolated and placed in culture with stromal cells and IL-7 some were able to differentiate into B220+ cells suggesting that within this population of cells resides a progenitor of the B cell lineage. The aberrant expression of these progenitor like cells in ethanol exposed neonatal mice may reveal a mechanism for the delay we observe in B cell development. It is the goal of this proposal to characterize the HSA1oB220- cell type, paying particular attention to the developmental capabilities both in vivo and in vitro.