TACI regulates IgA production by APRIL in collaboration with HSPG
TACI regulates IgA production by APRIL in collaboration with HSPG
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DOI：
10.1182/blood-2006-08-041772
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发表时间：
2007-04-01
期刊：
影响因子：
20.3
通讯作者：
Kobata, Tetsuji
中科院分区：
文献类型：
--
作者：
Sakurai, Daisuke;Hase, Hidenori;Kobata, Tetsuji
跨膜激活剂和钙调节剂和亲环素配体相互作用物（TACI）是肿瘤坏死因子（TNF）受体家族的成员，其充当TNF家族的B细胞激活因子（BAFF）的受体和增殖诱导配体（APRIL）。虽然TACI被报道为B细胞反应的正或负调节剂，但其作用仍然难以捉摸。使用TACI siRNA进入B细胞的实验表明，TACI与硫酸乙酰肝素蛋白聚糖（HSPG）协作正调控APRIL诱导的伊加产生。此外，TACI负调节BAFF诱导的B细胞增殖和伊加和IgG的产生。此外，用肝素酶处理B细胞以使HSPG变性表明，HSPG对于APRIL诱导的B细胞应答如B细胞增殖、IgG和伊加产生、诱导活化诱导的胞苷脱氨酶（AID）和非经典NF-κ B2是必需的。与此相反，磷酸化的生理AID激酶，蛋白激酶A（PKA），是依赖于TACI。重要的是，通过特异性抗体而不是通过TACI或HSPG连接本身的TACI和HSPG的共连接可以诱导PKA和伊加的磷酸化而不是APRIL的产生。我们的研究结果表明，同时结合的TACI和热休克蛋白G与APRIL的B细胞是至关重要的伊加生产。
Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is a member of the tumor necrosis factor (TNF) receptor family that serves as a receptor for B-cell activating factor of the TNF family (BAFF) and as a proliferation-inducing ligand (APRIL). Although TACI is reported to function as a positive or negative regulator for B-cell responses, its roles remain elusive. Experiments using TACI siRNA into B cells indicated that TACI positively regulated APRIL-induced IgA production in collaboration with heparan sulfate proteoglycans (HSPG). Furthermore, TACI negatively regulated BAFF-induced B-cell proliferation and production of IgA and IgG. In addition, B cells treated with heparitinase to denature HSPG showed that HSPG is essential for APRIL-induced B-cell responses such as B-cell proliferation, IgG and IgA production, induction of activation-induced cytidine deaminase (AID), and noncanonical NF-kappa B2. In contrast, phosphorylation of physiological AID kinase, protein kinase A (PKA), was dependent on TACI. Importantly, coligation of TACI and HSPG by specific antibodies, but not by TACI or HSPG ligation itself, could induce the phosphorylation of PKA and IgA production instead of APRIL. Our findings indicate that simultaneous binding of TACI and HSPG on B cells with APRIL is crucial for IgA production.