Evelyn P Sievert, Marissa C Franke, Kayla B Thomas, Yoseop Yoon, Yongsheng Shi, Roger Sciammas
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引用次数: 0
摘要
分化成浆细胞（PC）后，每秒可分泌 1 万个免疫球蛋白分子。这种非凡的能力需要 PC 转录决定因子的上调，这些转录决定因子可指定 PC 的命运、增加免疫球蛋白 mRNA 的合成、协调重链转录本从远端多聚腺苷酸化位点（PAS）到近端多聚腺苷酸化位点（PAS）的 3' 端替代处理，并重塑分泌途径。我们开发了一种双荧光蛋白报告小鼠，以前瞻性地研究转录后水平从膜锚定免疫球蛋白 M 到分泌型免疫球蛋白 M 的转变；μM-PAS 和 μS-PAS。我们观察到：（1）在 PC 分化过程中，μS-PAS 的使用率分级；（2）IRF4 和 Blimp-1 在增加μ丰度和μS-PAS 使用率方面分级发挥作用；（3）分级的μS 群体表达或不表达 Blimp-1。有趣的是，低μS和高μS及Blimp-1表达群体产生于不同的发育中间阶段，表现出不同的内质网特征。不同的细胞和μS-PAS命运轨迹可能对分泌途径的衍生化有影响。
Distinct plasmablast developmental intermediates produce graded expression of IgM secretory transcripts.
Differentiation into plasma cells (PCs) enables secretion of ∼10,000 immunoglobulin molecules per second. This extraordinary capacity requires the upregulation of PC transcriptional determinants that specify PC fate, increase immunoglobulin mRNA synthesis, coordinate alternative 3' end processing of the heavy chain transcript from the distal to proximal polyadenylation site (PAS), and remodel the secretory pathway. We developed a dual-fluorescent protein reporter mouse to prospectively study the post-transcriptional-level transition from membrane anchored to secretory immunoglobulin M; μM-PAS and μS-PAS, respectively. We observed (1) graded μS-PAS usage during PC differentiation, (2) IRF4 and Blimp-1 functioned hierarchically to increase μ abundance as well as μS-PAS usage, and (3) graded μS populations did or did not express Blimp-1. Interestingly, the low and high μS and Blimp-1-expressing populations arose from distinct developmental intermediates that exhibited dissimilar endoplasmic reticulum features. The distinct cell and μS-PAS fate trajectories may have implications for derivatization of the secretory pathway.
期刊介绍：
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