Department of Emergency Medicine, JPS Health Network, 1500 S. Main Street, Fort Worth, TX 76104, USA.
Alcohol Alcohol. 2011 Jan-Feb;46(1):26-32. doi: 10.1093/alcalc/agq076. Epub 2010 Nov 22.
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.
Oligoclonal-neonatal-progenitor (ONP) cells from bone marrow cells of 2-week-old mice were cultured under different conditions in vitro with 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.
After 3 days in vitro culture, 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.
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.
先前的研究表明，酒精暴露会影响祖 B 细胞的分化。在最终确定 B 细胞谱系之前，祖 B 细胞通常要经历几个重要阶段。然而，目前尚不清楚酒精是否会改变 B 细胞分化的哪个阶段。本研究旨在确定酒精影响祖细胞分化的哪个（些）阶段，并阐明酒精对 B 细胞分化影响的机制。
从小鼠 2 周龄骨髓细胞中培养出寡克隆-新生祖细胞（ONP）细胞，在不同条件下进行体外培养，有或没有暴露于 100mM 酒精。在不同时间点进行表型分析，并定量和动态测量转录因子（TFs）和细胞因子受体的表达水平。
在体外培养 3 天后，ONP 细胞分化为两个群体：B220(-)CD11b(-)和 B220(-)CD11b(+)细胞。B220(-)CD11b(-)细胞只有在 B220(-)CD11b(+)细胞的支持下才能进一步分化为 B 细胞系。在培养的前 3 天内暴露于 100mM 酒精的细胞在第 12 天与对照组相比，B 细胞形成没有统计学差异。然而，从第 4 天开始暴露于酒精直至培养结束的细胞产生的 B 细胞非常少。在添加 100mM 酒精的情况下，ONP 细胞共培养时 TFs 和细胞因子受体的表达水平呈动态下调。
酒精影响 ONP 细胞向 B 细胞谱系的晚期分化。酒精还下调 TFs 和细胞因子受体的表达水平，导致 B 细胞分化受损。
