Transgelin-2 is upregulated on activated B-cells and expressed in hyperplastic follicles in lupus erythematosus patients.
Transgelin-2 is upregulated on activated B-cells and expressed in hyperplastic follicles in lupus erythematosus patients.
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DOI：
10.1371/journal.pone.0184738
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Miyagawa-Hayashino A
中科院分区：
文献类型：
--
作者：
Kiso K;Yoshifuji H;Oku T;Hikida M;Kitagori K;Hirayama Y;Nakajima T;Haga H;Tsuruyama T;Miyagawa-Hayashino A
Transgelin-2（TAGLN 2）是一种肌动蛋白结合蛋白，其控制肌动蛋白稳定性并促进T细胞活化。TAGLN 2也在B细胞上表达，但其在B细胞中的功能尚不清楚。我们发现表达TAGLN 2的B细胞定位于次级淋巴组织的生发中心（GC），并且在原代人B细胞中，在IgM+IgG刺激后，TAGLN 2 mRNA显著上调，表明TAGLN 2在B细胞活化后上调。为了支持这一点，与对照淋巴结相比，来自系统性红斑狼疮（SLE）患者的淋巴结（LN）（其中已识别出强烈的GC活性）显示出B细胞中TAGLN 2表达增加。此外，TAGLN 2 + B细胞不仅广泛分布在GC中，而且还广泛分布在SLE LN的滤泡周围区域。与此相反，SLE患者外周血中的CD 19 + B细胞和CD 19 + CD 27+记忆B细胞显示TAGLN 2 mRNA没有增加。Raji细胞的双光子激发显微镜表明，TAGLN 2与F-肌动蛋白共定位，并在刺激后一起移动到外周。Raji细胞中TAGLN 2敲低导致PLCγ2磷酸化受损，从而抑制细胞迁移。TAGLN 2敲除Raji细胞的微阵列分析显示，与对照组相比，与免疫功能相关的基因（包括CCR 6）以及与肌动蛋白细胞骨架调节相关的基因（包括ABI 2）的表达降低。这些结果表明，TAGLN 2可能调节B细胞的活化和迁移，特别是活化的B细胞进入卵泡。我们还建议TAGLN 2可以用作活化B细胞的标志物。
Transgelin-2 (TAGLN2) is an actin-binding protein that controls actin stability and promotes T cell activation. TAGLN2 is also expressed on B-cells but its function in B-cells is unknown. We found that TAGLN2-expressing B-cells were localized in the germinal center (GC) of secondary lymphoid tissues and TAGLN2 mRNA was significantly upregulated after IgM+IgG stimulation in primary human B-cells, suggesting that TAGLN2 was upregulated upon B-cell activation. In support of this, lymph nodes (LNs) from patients with systemic lupus erythematosus (SLE), in which the intense GC activity have been recognized, showed increased TAGLN2 expression in B-cells compared to control LNs. Moreover, TAGLN2+B-cells were distributed widely not only in the GC but also in the perifollicular areas in SLE LNs. In contrast, CD19+ B-cells and CD19+CD27+ memory-B cells in peripheral blood of SLE patients showed no increase in TAGLN2 mRNA. Two-photon excitation microscopy of Raji cells demonstrated that TAGLN2 colocalized with F-actin and moved together to the periphery upon stimulation. TAGLN2-knockdown in Raji cells resulted in impaired phosphorylation of PLCγ2 leading to inhibition of cell migration. Microarray analysis of TAGLN2-knockdown Raji cells showed decreased expression of the genes associated with immune function including CCR6 and as well as of those associated with regulation of the actin cytoskeleton including ABI2, compared to controls. These results suggest that TAGLN2 might regulate activation and migration of B-cells, in particular, the entry of activated B-cells into the follicle. We also suggest that TAGLN2 could be used as a marker for activated B-cells.