IFN-α amplifies human naive B cell TLR-9-mediated activation and Ig production
IFN-α amplifies human naive B cell TLR-9-mediated activation and Ig production
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DOI：
10.1189/jlb.0908560
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发表时间：
2009-08-01
影响因子：
5.5
通讯作者：
Viora, M.
中科院分区：
文献类型：
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作者：
Giordani, L.;Sanchez, M.;Viora, M.
TLR是作为用于检测病原体的传感器起作用的分子家族。TLR-9在B细胞和pDC上表达，识别未甲基化的细菌DNA的CpG基序，并在自身免疫的发展中起作用。本研究旨在研究IFN-α联合CpG ODN对CD 27-naive B细胞活化和IG产生的影响。我们提供的证据表明，CpG ODN不仅诱导总的和T-依赖性的，特异性IgM应答的幼稚B细胞，但也在浆细胞中的表型分化，所示的上调CD 38的表达。我们发现用CpG ODN刺激TLR-9可诱导IL-1 β、TNF-α、IL-10和IL-6的产生。有趣的是，我们还发现CpG ODN诱导幼稚B细胞成熟为记忆细胞，如通过诱导CD 27、AID mRNA表达和IgG产生所证明的。更重要的是，我们的研究结果表明，IFN-α放大了CpG ODN对幼稚B活化和IG产生的诱导作用，通过TLR-9/MyD 88依赖性信号传导机制。此外，我们发现IFN-alpha增强了CpG ODN诱导的记忆B细胞的频率。我们的研究结果可能有助于澄清通过TLR-9促进IFN-α诱导的幼稚B细胞活化扩增的事件，以更好地理解自身免疫性疾病的发病机制，并可能指导针对B细胞内这一途径的治疗。J. Leukoc. 86：261-271; 2009.
TLRs are a family of molecules that function as sensors for the detection of pathogens. TLR-9, expressed on B cells and pDCs, recognizes CpG motifs of unmethylated bacterial DNA and plays a role in the development of autoimmunity. The present study was designed to investigate the effects of IFN-alpha in combination with CpG ODN on the activation of CD27-naive B cells and on Ig production. We provide evidence that CpG ODN not only induces a total and T-dependent, specific IgM response by naive B cells but also their phenotypic differentiation in plasma cells, as demonstrated by the upregulation of CD38 expression. We found that TLR-9 stimulation with CpG ODN induces IL-1 beta, TNF-alpha, IL-10, and IL-6 production. Interestingly, we also found that CpG ODN induces naive B cell maturation into memory cells, as demonstrated by the induction of CD27, AID mRNA expression, and IgG production. More importantly, our results demonstrate that IFN-alpha amplifies the inductive effect of CpG ODN on naive B activation and on Ig production through a mechanism involving TLR-9/MyD88-dependent signaling. Moreover, we found that IFN-alpha enhances the frequency of CpG ODN-induced memory B cells. Our results may contribute to clarify the events promoting IFN-alpha-induced amplification of naive B cell activation via TLR-9 for a better understanding of the pathogenesis of autoimmune disorders and may guide treatments targeting this pathway within B cells. J. Leukoc. Biol. 86: 261-271; 2009.