The radioprotective 105/MD-1 complex links TLR2 and TLR4/MD-2 in antibody response to microbial membranes
The radioprotective 105/MD-1 complex links TLR2 and TLR4/MD-2 in antibody response to microbial membranes
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DOI：
10.4049/jimmunol.174.11.7043
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发表时间：
2005-06-01
影响因子：
4.4
通讯作者：
Miyake, K
中科院分区：
文献类型：
--
作者：
Nagai, Y;Kobayashi, T;Miyake, K
针对微生物膜的低亲和力IgG3抗体对微生物的初级免疫防御很重要，但人们对TLRs在其生产中的重要性知之甚少。在缺乏放射防护105(RP105)的小鼠中，IgG3水平极低。RP105是一种B细胞表面分子，结构上与TLRs相关。RP105(-/-)B细胞对TLR4配体脂蛋白和TLR2配体脂蛋白的反应都很差，两者都介导了微生物膜的免疫刺激活性。RP105(-/-)小鼠在产生抗脂蛋白或脂蛋白的半抗原特异性抗体方面受到严重损害。注射脂质A后，野生型小鼠脾组织中检测到CD138(syndecan-1)阳性浆细胞，而RP105(-/-)小鼠脾组织中CD138(syndecan-1)阳性浆细胞明显减少。RP105体内结扎诱导浆细胞分化。RP105在边缘带B细胞的表达比滤泡细胞和B1细胞高3倍左右，在生发中心细胞表达下调。这些结果表明，通过RP105的信号对于调节微生物膜上TLR依赖的抗体的产生是唯一重要的。
Low-affinity IgG3 Abs to microbial membranes are important for primary immune defense against microbes, but little is known about the importance of TLRs in their production. IgG3 levels were extremely low in mice lacking radioprotective 105 (RP105), a B cell surface molecule structurally related to TLRs. RP105(-/-) B cells proliferated poorly in response to not only the TLR4 ligand LPS but also TLR2 ligand lipoproteins, both of which mediate the immunostimulatory activity of microbial membranes. RP105(-/-) mice were severely impaired in hapten-specific Ab production against LPS or lipoproteins. CD138 (syndecan-1)-positive plasma cells were detected after lipid A injection in wild-type spleen but much less in RP105(-/-) spleen. RP105 ligation in vivo induced plasma cell differentiation. RP105 expression was similar to 3-fold higher on marginal zone B cells than on follicular and B1 cells and was down-regulated on germinal center cells. These results demonstrate that a signal via RP105 is uniquely important for regulating TLR-dependent Ab production to microbial membranes.