Vitamin A and immune function: Retinoic acid modulates population dynamics in antigen receptor and CD38-stimulated splenic B cells
Vitamin A and immune function: Retinoic acid modulates population dynamics in antigen receptor and CD38-stimulated splenic B cells
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DOI：
10.1073/pnas.0505018102
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发表时间：
2005-10-04
影响因子：
11.1
通讯作者：
Ross, AC
中科院分区：
文献类型：
--
作者：
Chen, QY;Ross, AC
维生素A及其活性代谢物全反式维甲酸(RA)在体内调节抗体反应，尽管其潜在机制尚不清楚。我们研究了维甲酸对B细胞抗原受体(BCR)和/或BCR辅受体CD38刺激的纯化小鼠B细胞的B细胞群体动力学和Ig基因表达的调节。在结扎BCR和/或CD38后，B细胞的大小变得更加不均匀。RA在很大程度上抑制了这种变化，并伴随着细胞增殖的抑制。为了更好地检测B细胞的异质性，我们根据大小(前向光散射)对刺激的B细胞进行了分类，并测定了细胞分裂动力学、生殖系Ig重链基因转录和表面lgG1(SlgG1)的表达。流式细胞仪对标记slgG1的B细胞的流式细胞术分析显示，增殖越强的B细胞群越小，而表达更多slgG1的细胞越大。RA丰富了后者的群体，而细胞分裂频率和经历过分裂周期的较小B细胞的数量总体上减少了。尽管RA显著抑制了总B细胞群中的Ig生殖系转录水平，但代表更具分化表型的CD19(-)IgG1+B细胞得到了丰富。此外，RA刺激的B细胞中PAX-5基因表达降低，活化诱导的胞苷脱氨酶基因表达增加。因此，RA调节已知的Ig类开关重组所需的因子，并调节结扎刺激的B细胞的种群动态，同时促进部分B细胞的进展。分化成表达sLGG的细胞。
Vitamin A and its active metabolite, all-trans retinoic acid (RA), regulate the antibody response in vivo, although the underlying mechanisms are not well understood. We have investigated the regulation by RA of B cell population dynamics and Ig gene expression in purified splenic mouse B cells stimulated through the B cell antigen receptor (BCR) and/or CD38, a BCR coreceptor. After ligation of the BCR and/or CD38, B cells became more heterogeneous in size. RA substantially restrained this change, concomitant with inhibition of cell proliferation. To examine B cell heterogeneity more closely, we categorized stimulated B cells by size (forward angle light scatter) and determined cell division dynamics, germ-line Ig heavy chain gene transcription and surface lgG1 (slgG1) expression. Flow cytometric analysis of carboxyfluorescein diacetate succinimidyl ester-labeled B cells costained for slgG1 showed that the more proliferative groups of B cells were smaller, whereas cells expressing more slgG1 were larger. RA enriched the latter population, whereas cell division frequency in general and the number of smaller B cells that had undergone division cycles were reduced. Although RA significantly inhibited Ig germ-line transcript levels in the total B cell population, CD19(-)IgG1+ B cells, which represent a more differentiated phenotype, were enriched. Furthermore, pax-5 mRNA was decreased and activation-induced cytidine deaminase mRNA was increased in RA-treated stimulated B cells. Thus, RA regulated factors known to be required for Ig class switch recombination and modulated the population dynamics of ligation-stimulated B cells, while promoting the progression of a fraction of B cells. into differentiated slgG-expressing cells.