Deficiency of mannose-binding lectin greatly increases antibody response in a mouse model of vaccination

Deficiency of mannose-binding lectin greatly increases antibody response in a mouse model of vaccination
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DOI:
10.1016/j.clim.2008.09.012
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发表时间:
2009-03-01
影响因子:
8.6
通讯作者:
Takahashi, Kazue
Takahashi, Kazue
中科院分区:
医学3区
文献类型:
--
作者:
Guttormsen, Hilde-Kari;Stuart, Lynda M.;Takahashi, Kazue

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甘露糖结合凝集素(MBL)是一种模式识别的天然免疫分子,可选择性地结合不同的化学物质。模式,包括碳水化合物上表达的8组链球菌(GBS)。MBL与IgM相互作用,导致MBL相关丝氨酸蛋白酶(MASP)的活化,从而启动凝集素补体途径。补体蛋白和IgM调节抗原特异性抗体的产生。在这项研究中,我们研究了MBL在破伤风类毒素结合GBS多糖疫苗(GBS PS-TT)的抗体应答中的相对作用,通过比较野生型和裸小鼠的MBL,补体3(0),IgM,MBL/C3和MBL/IgM。我们发现,在用GBS PS-TT而不是GBS PS免疫后,MBL缺陷小鼠中GBS PS特异性IgG应答上调。B1细胞在MBL基因敲除小鼠的腹膜中扩增,但在脾脏中不扩增。MBL基因敲除小鼠IgG反应增强的机制与C3有关,与IgM有相同的途径。(C)2008 Etsevier Inc. All rights reserved.
Mannose-binding lectin (MBL), a pattern recognition innate immune molecule, selectively binds distinct chemical. patterns, including carbohydrates expressed on Group 8 streptococcus (GBS). MBL interacts with IgM, resulting in the activation of MBL-associated serine proteases (MASPs), thus is initiating a lectin complement pathway. Complement proteins and IgM modulate production of antigen specific antibody. In this study, we investigated the relative effect of MBL in antibody response against tetanus toxoid-conjugated GBS polysaccharide vaccines (GBS PS-TT) by comparing wild type and null mice for MBL, complement 3 (0), IgM, MBL/C3, and MBL/IgM. We found that GBS PS specific IgG response was upregulated in MBL deficient mice following immunization with GBS PS-TT but not GBS PS. B1 cells were expanded in peritonium but not in spleen of MBL null mice. The mechanisms of heightened IgG response in MBL null mice were related to C3, and share the same pathway with IgM. (C) 2008 Etsevier Inc. All rights reserved.