Signaling pathways for B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in human placenta

Signaling pathways for B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in human placenta
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DOI:
10.2353/ajpath.2008.071139
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发表时间:
2008-05-01
影响因子:
6
通讯作者:
Hunt, Joan S.
Hunt, Joan S.
中科院分区:
医学2区
文献类型:
--
作者:
Langat, Daudi L.;Wheaton, David A.;Hunt, Joan S.

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肿瘤坏死超家族(TNFSF)包括两个参与B淋巴细胞发育的可溶性配体,BAFF(B细胞激活因子,BLyS,TALL-1,CD257,TNFSF13B)和APRIL(增殖诱导配体,CD256,TNFSF13)。这两种配体通过三种受体传递信号:BAFF受体(BAFF-R,CD268,TNFRSF17)和识别BAFF和APRIL的两种受体,TACI(跨膜激活剂-1和钙调节剂-和亲环素配体相互作用CD267,TNFRSF13B)和BCMA(B细胞成熟抗原,CD269,TNFRSF13C)。除BAFF-R外,其余均在足月胎盘中合成。在这项研究中,配体和受体在胎盘细胞的两个不同亚群,葡萄胎细胞滋养细胞(VCTB)和间充质细胞(MC)中的表达有差异。实时定量聚合酶链式反应显示vCTB细胞低水平表达BAFF和APRIL转录本,而MCs高水平表达BAFF和APRIL转录产物。实时定量聚合酶链式反应和免疫组织化学均检测到vCTB细胞中BAFF-R和BCMA的mRNA和蛋白表达,但基本上未检测到TACI。相比之下,MC中所有三种受体的水平都很容易被检测到。这些结果揭示了BAFF和APRIL信号在人胎盘中潜在的自分泌和旁分泌途径,提示胎盘细胞活性、分化和/或其他活动的谱系特异性调节可能是这些蛋白的新功能。
The tumor necrosis superfamily (TNFSF) contains two soluble ligands that are involved in B lymphocyte development, BAFF (B cell activating factor, BlyS, TALL-1, CD257, TNFSF13B) and APRIL (a proliferation inducing ligand, CD256, TNFSF13). These two ligands signal through three receptors: the exclusive BAFF receptor (BAFF-R, CD268, TNFRSF17) and two receptors that recognize both BAFF and APRIL, TACI (transmembrane-activator-1 and calcium-modulator- and cyclophilin ligand-interactor CD267, TNFRSF13B) and BCMA (B cell maturation antigen, CD269, TNFRSF13C). All but BAFF-R are known to be synthesized in term placentas. In this study, expression of the ligands and receptors were distinguished in two embryologically discrete subpopulations of placental cells, vinous cytotrophoblast (vCTB) cells and mesenchymal cells (MCs). Real-Time PCR showed that vCTB cells contain low levels of BAFF and APRIL transcripts whereas MCs contain high levels. Both Real-Time PCR and immunohistochemistry identified BAFF-R and BCMA mRNA and proteins in vCTB cells but essentially no TACI. By contrast, MCs contained readily detectable levels of all three receptors. These results illustrating potential autocrine and paracrine pathways for BAFF and APRIL signaling in human placentas suggest that lineage-specific regulation of placental cell viability, differentiation and/or other activities maybe novel functions of these proteins.