Alcohol affects the late differentiation of progenitor B cells.
Alcohol affects the late differentiation of progenitor B cells.
复制标题
酒精会影响祖 B 细胞的晚期分化。
DOI：
10.1093/alcalc/agq076
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Wolcott,Michael
中科院分区：
文献类型：
--
作者：
Wang,Hao;Zhou,Huijuan;Mahler,Simon;Chervenak,Robert;Wolcott,Michael
目的：以往的研究表明，酒精暴露可以影响祖B细胞的分化。在最终定型为B谱系之前，祖B细胞通常经历几个重要阶段。然而，目前还不清楚酒精是否会改变B细胞在哪个阶段的分化。本研究的目的是确定哪些阶段的祖细胞分化受到酒精的影响，并阐明机制（S）负责的酒精对B细胞分化的影响。方法：从2周龄小鼠骨髓细胞中分离的寡克隆新生儿祖细胞（ONP）细胞在不同条件下体外培养，有或没有暴露于100 mM酒精。结果：体外培养3d后，ONP细胞分化为B220− CD 11b −和B220− CD 11b+两种细胞群。B220− CD 11 B −细胞仅在B220− CD 11 B+细胞的支持下才能进一步分化为B谱系细胞。与对照组相比，在培养的前3天暴露于100 mM乙醇的细胞在12天后的B细胞形成中没有显示出统计学上的显著差异。然而，从第4天到培养结束暴露于酒精的细胞产生非常少的B细胞。结论：酒精在晚期影响ONP细胞向B系分化。酒精还下调TF和细胞因子受体的表达水平，导致B细胞分化受损。
Aims:Previous studies show that alcohol exposure can affect the differentiation of progenitor B cells. Before final commitment to a B lineage, progenitor B cells usually undergo several important stages. However, it is still unclear whether alcohol alters B cell differentiation at which stages. The aim of this study was to determine which stage(s) of progenitor cell differentiation are affected by alcohol and to elucidate the mechanism(s) responsible for the effect of alcohol on B cell differentiation.Methods:Oligoclonal-neonatal-progenitor (ONP) cells from bone marrow cells of 2-week-old mice were cultured under different conditionsin vitrowith or without the exposure of 100 mM alcohol. Phenotype analysis was performed at different time points and expression levels of transcription factors (TFs) and cytokine receptors were measured quantitatively and kinetically.Results:After 3 daysin vitroculture, ONP cells differentiated into two populations: B220−CD11b−and B220−CD11b+cells. B220−CD11b−cells can further differentiate into B lineage cells only with the support of B220−CD11b+cells. Cells exposed to 100 mM of alcohol during the first 3 days of culture showed no statistically significant difference in B cell formation after 12 days compared with the control group. However, cells exposed to alcohol from Day 4 till the end of culture yield very few B cells. Expression levels of TFs and cytokine receptors were down-regulated kinetically among ONP cells co-cultured with the addition of 100 mM alcohol.Conclusions:Alcohol affects the ONP cell differentiation into B lineage at a late stage. Alcohol also down-regulates the expression level of TFs and cytokine receptors resulting in the impairment of B cell differentiation.