Cutting edge: Innate Immunity conferred by B cells is regulated by caspase-8
Cutting edge: Innate Immunity conferred by B cells is regulated by caspase-8
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DOI：
10.4049/jimmunol.175.6.3469
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发表时间：
2005-09-15
影响因子：
4.4
通讯作者：
Hedrick, SM
中科院分区：
文献类型：
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作者：
Beisner, DR;Ch'en, IL;Hedrick, SM
Caspase-8是死亡受体介导的细胞凋亡的重要组成部分。与Fas相关的死亡结构域蛋白一样，它对T细胞在抗原或有丝分裂刺激下的增殖也是必不可少的。为了确定Caspase-8是否也是B细胞增殖所必需的，我们培育了B细胞特异性Casp8缺乏的小鼠。与T细胞不同，caspase-8不是Ag受体驱动的增殖或抗体形成所必需的。相反，Casp8缺陷的B细胞不能对dsRNA和LPS(分别是TLR3和TLR4的配体)产生增殖反应，但对TLR9激动剂CpG DNA的反应正常。同样，在B细胞特异性Casp8缺陷小鼠中，对三硝基苯酚-内毒素的抗体产生选择性地减少。核因子-kappa B或干扰素调节因子3的激活不受caspase-8丢失的影响，这意味着它在由B细胞介导的某些形式的天然免疫中具有重要的新途径。
Caspase-8 is an essential component of death receptor-mediated apoptosis. Along with Fas-associated death domain protein, it is also essential for T cell proliferation in response to antigenic or mitogenic stimuli. To determine whether caspase-8 is also required for B cell proliferation, we generated mice with a B cell-specific Casp8 deficiency. Unlike T cells, caspase-8 was not required for Ag receptor-driven proliferation or Ab formation. Rather, Casp8-deficient B cells failed to proliferate in response to dsRNA and LPS, ligands for TLR3 and TLR4, respectively, but responded normally to the TLR9 agonist CpG DNA. Similarly, Ab production to trinitrophenol-LPS was selectively reduced in B cell-specific Casp8-deficient mice. The activation of NF-kappa B or IFN regulatory factor 3 was found to be unaffected by the loss of caspase-8, implicating it in a novel pathway important for some forms of innate immunity mediated by B cells.