Fcµ Receptor Promotes the Survival and Activation of Marginal Zone B Cells and Protects Mice against Bacterial Sepsis.
Fcµ Receptor Promotes the Survival and Activation of Marginal Zone B Cells and Protects Mice against Bacterial Sepsis.
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Fc mu 受体促进边缘区 B 细胞的存活和激活并保护小鼠免受细菌性败血症
DOI：
10.3389/fimmu.2018.00160
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发表时间：
2018
影响因子：
7.3
通讯作者：
Wang JY
中科院分区：
文献类型：
--
作者：
Liu J;Zhu H;Qian J;Xiong E;Zhang L;Wang YQ;Chu Y;Kubagawa H;Tsubata T;Wang JY
边缘区B细胞（MZ B）位于循环和淋巴组织之间的界面，在先天性和适应性免疫应答中起重要作用。我们以前发现MZB在IgM Fc受体（FcμR）缺陷的小鼠中显著减少，但FcμR如何调节MZB的发育和功能仍不清楚。在这项研究中，我们发现FcμR−/−小鼠的边缘区前体（MZP）和MZB均减少。MZP和MZB的减少不是由于这些细胞的增殖受损，而是由于它们的死亡增加。进一步分析显示，FcμR−/− MZB具有降低的强直性BCR信号，如其相对于WT MZB降低的磷酸化SYK和AKT水平所证明的。与WT小鼠中的MZB相比，FcμR−/−小鼠中的MZB对体内LPS的反应较差。与MZB比例降低及其对LPS的反应受损一致，FcμR−/−小鼠中针对1型T非依赖性Ag（NP-LPS）的抗体产生显著降低。此外，FcμR−/−小鼠对枸橼酸杆菌诱导的败血症高度易感。这些结果揭示了FcμR在MZB的存活和激活以及对急性细菌感染的保护中的关键作用。
The marginal zone B cells (MZB) are located at the interface between the circulation and lymphoid tissue and as a gatekeeper play important roles in both innate and adaptive immune responses. We have previously found that MZB are significantly reduced in mice deficient in the IgM Fc receptor (FcμR) but how FcμR regulates the development and function of MZB remains unknown. In this study, we found that both marginal zone precursor (MZP) and MZB were decreased in FcμR−/− mice. The reduction of MZP and MZB was not due to impaired proliferation of these cells but rather due to their increased death. Further analysis revealed that FcμR−/− MZB had reduced tonic BCR signal, as evidenced by their decreased levels of phosphorylated SYK and AKT relative to WT MZB. MZB in FcμR−/− mice responded poorly to LPS in vivo when compared with MZB in WT mice. Consistent with the reduced proportion of MZB and their impaired response to LPS, antibody production against the type 1 T-independent Ag, NP-LPS, was significantly reduced in FcμR−/− mice. Moreover, FcμR−/− mice were highly susceptible to Citrobacter rodentium-induced sepsis. These results reveal a critical role for FcμR in the survival and activation of MZB and in protection against acute bacterial infection.
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发表时间：
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期刊：
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影响因子：
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作者：
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发表时间：
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期刊：
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影响因子：
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