Department of Molecular Pathology, Institute of Pathology, Comprehensive Cancer Center (CCC) Mainfranken, University of Würzburg, Würzburg, Germany.
Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University, Okayama, Japan.
Front Immunol. 2018 Jan 24;9:32. doi: 10.3389/fimmu.2018.00032. eCollection 2018.
In lymphocytes, immune receptor signals induce the rapid nuclear translocation of preformed cytosolic NFAT proteins. Along with co-stimulatory signals, persistent immune receptor signals lead to high levels of NFATc1/αA, a short NFATc1 isoform, in effector lymphocytes. Whereas NFATc1 is not expressed in plasma cells, in germinal centers numerous centrocytic B cells express nuclear NFATc1/αA. When overexpressed in chicken DT40 B cells or murine WEHI 231 B cells, NFATc1/αA suppressed their cell death induced by B cell receptor signals and affected the expression of genes controlling the germinal center reaction and plasma cell formation. Among those is the gene encoding Blimp-1, a key factor of plasma cell formation. By binding to a regulatory DNA element within exon 1 of the gene, NFATc1/αA suppresses Blimp-1 expression. Since expression of a constitutive active version of NFATc1/αA interfered with RNA expression, LPS-mediated differentiation of splenic B cells to plasmablasts and reduced immunoglobulin production , one may conclude that NFATc1/αA plays an important role in controlling plasmablast/plasma cell formation.
在淋巴细胞中，免疫受体信号诱导预先形成的细胞质 NFAT 蛋白快速核易位。与共刺激信号一起，持续的免疫受体信号导致效应淋巴细胞中高水平的 NFATc1/αA，一种短的 NFATc1 同工型。虽然 NFATc1 不在浆细胞中表达，但在生发中心中，许多中心性 B 细胞表达核 NFATc1/αA。当在鸡 DT40 B 细胞或鼠 WEHI 231 B 细胞中过表达时，NFATc1/αA 抑制了由 B 细胞受体信号诱导的细胞死亡，并影响了控制生发中心反应和浆细胞形成的基因的表达。其中包括编码 Blimp-1 的基因，Blimp-1 是浆细胞形成的关键因素。NFATc1/αA 通过结合基因 1 号外显子内的调节 DNA 元件，抑制 Blimp-1 的表达。由于组成性激活形式的 NFATc1/αA 的表达干扰了 RNA 的表达，LPS 介导的脾脏 B 细胞向浆母细胞的分化 以及免疫球蛋白产生的减少 ，人们可以得出结论，NFATc1/αA 在控制浆母细胞/浆细胞形成中发挥重要作用。
