The RP105/MD-1 complex is indispensable for TLR4/MD-2-dependent proliferation and IgM-secreting plasma cell differentiation of marginal zone B cells
The RP105/MD-1 complex is indispensable for TLR4/MD-2-dependent proliferation and IgM-secreting plasma cell differentiation of marginal zone B cells
复制标题
RP105/MD-1复合物对于边缘区B细胞的TLR4/MD-2依赖性增殖和分泌IgM的浆细胞分化是不可或缺的
DOI：
10.1093/intimm/dxs040
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发表时间：
2012
影响因子：
4.4
通讯作者：
Yoshinori Nagai
中科院分区：
文献类型：
--
作者：
Tsukamoto H;Fukudome K;Takao S;Tsuneyoshi N;Ohta S;Nagai Y;Ihara H;Miyake K;Ikeda Y;Kimoto M;Yoshinori Nagai
边缘带(MZ)B细胞快速启动T细胞非依赖性(T-I)免疫反应，对抗微生物成分，如脂多糖。虽然Toll样受体4(TLR4)对于内毒素反应是必不可少的，但MZ B细胞独特地表达高水平的另一种内毒素感受器辐射防护105(RP105)。然而，关于RP105是如何被MZ B细胞利用的，人们知之甚少。在这项研究中，我们研究了依赖TLR4或RP105的MZ B细胞的反应，利用针对每个受体的激动型单抗(MAbs)。将TLR4和RP105与单抗同时交联，可诱导产生大量分泌IgM的浆细胞，作为脂蛋白A部分的脂多糖。相反，单独使用任何一种单抗刺激都不能引起这样的反应。RP105基因缺陷的MZ B细胞不能产生分泌IgM的浆细胞，TLR4或LipA刺激MZ B细胞上调其B淋巴细胞诱导成熟蛋白1(Blimp-1)和X盒结合蛋白1(XBP-1)的mRNA表达。单独刺激RP105不能给出这些反应，事实上减少了TLR4介导的它们的表达。与野生型(WT)MZB细胞相比，RP105缺陷的MZB细胞在脂质A刺激下Blimp-1和XBP-1mRNA的表达增加，而RP105缺陷的MZB细胞不能诱导Bclxl和c-Myc的表达。这些反应参与了TLR4介导的MZ B细胞的抗凋亡反应。因此，RP105在依赖TLR4的MZ B细胞的存活、增殖和浆细胞生成中起着独特的作用。
Marginal zone (MZ) B cells mount rapid T-cell-independent (T-I) immune responses against microbial components such as LPS. While Toll-like receptor 4 (TLR4) is essential for LPS responses, MZ B cells uniquely express high levels of another LPS sensor Radioprotective 105 (RP105). However, little is known about how RP105 is used by MZ B cells. In this study, we investigated TLR4- or RP105-dependent MZ B cell responses by utilizing agonistic monoclonal antibodies (mAbs) to each receptor. Cross-linking TLR4 and RP105 at the same time with the mAbs induced robust IgM-secreting plasma cell generation as lipid A moiety of LPS. In contrast, stimulation with either mAb alone did not elicit such responses. RP105-deficient MZ B cells failed to produce IgM-secreting plasma cells in response to lipid A. TLR4 or lipid A stimulation of MZ B cells up-regulated their B lymphocyte-induced maturation protein 1 (Blimp-1) and X-box-binding protein 1 (Xbp-1) mRNA expression. RP105 stimulation alone did not give these responses and in fact decreased TLR4-mediated their expression. Compared with wild-type (WT) MZ B cells, RP105-deficient MZ B cells exhibited increased levels of Blimp-1 and Xbp-1 mRNA expression in response to lipid A. Lipid A or TLR4 plus RP105 stimulation induced massive proliferation and expression of Bcl-xL and c-Myc in WT but not RP105-deficient MZ B cells. These responses contributed to TLR4-mediated anti-apoptotic responses in MZ B cells. Thus, RP105 contributes in a unique way to the TLR4-dependent survival, proliferation and plasma cell generation of MZ B cells.