Ｂリンパ球の分化と自己免疫に関するマウスｇｐ４９Ｂの機能解析

小鼠gp49B在B淋巴细胞分化和自身免疫方面的功能分析

• 批准号: 16J01922
• 负责人: WONG YI LI
• 金额: $ 1.22万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2016
• 资助国家: 日本
• 起止时间: 2016-04-22 至 2019-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16J01922/
• 关键词: glycoprotein 49B; SLE; plasma cell; autoimmunity; pathogenic antibody; gp49B

gp49b deficiency in BXSB/Yaa mice reduced serum titer of anti-dsDNA IgG and prolonged survival rate with mild kidney inflammation. gp49B-deficient BXSB/Yaa mice have regained marginal zone B cells and slight reduction of monocytosis. These observations suggested a pathogenic role of gp49B in SLE disease.BXSB/Yaa mice treated with anti-gp49 monoclonal antibody showed suppression of increase in serum titer of anti-dsDNA IgG, without any cells depletion (including number of pathogenic cells).gp49B deficiency in aged FcgammaRIIB-knockout SLAM129(RIIB-/-) female mice showed heightened autoimmunity, with lesser longevity and more switched memory B cells. The difference between BXSB/Yaa and RIIB-/- mice could be the amplification effect of gp49B deficiency to tolerance loss from RIIB deficiency.

BXSB/YAA小鼠gp49b缺乏可降低血清抗dsDNA免疫球蛋白滴度，延长存活率，并伴有轻度肾脏炎症。Gp49B基因缺陷的BXSB/YAA小鼠恢复了边缘带B细胞，单核细胞数略有减少。这些观察表明gp49B在SLE疾病中起致病作用。经抗gp49单抗处理的BXSB/Yaa小鼠表现出抑制血清抗dsDNA抗体滴度的增加，而没有任何细胞耗竭(包括致病细胞数量)。在老年FcGammaRIIB基因敲除SLAM129(RIIB-/-)雌性小鼠中，gp49B缺乏表现出较高的自身免疫力，寿命较短，切换记忆B细胞较多。BXSB/YaA和RIIB-/-小鼠之间的差异可能是gp49B缺陷对RIIB缺陷所致的耐受性丧失的放大作用。

项目成果

Expression of gp49B on plasma cells from autoimmune-prone mice and its relevance to progression of autoimmune disease

gp49B 在易患自身免疫的小鼠浆细胞上的表达及其与自身免疫性疾病进展的相关性

• 发表时间: 2017
• 作者: Yi Li Wong;Masanori Inui;Toshiyuki Takai
• 通讯作者: Toshiyuki Takai

Glycoprotein 49B (gp49B) as a pathogenic marker for antibody-secreting cells in lupus-prone mice

糖蛋白 49B (gp49B) 作为狼疮易感小鼠抗体分泌细胞的致病标记

• 发表时间: 2019
• 作者: Wong Yi Li;Su Mei-Tzu;Inui Masanori;Takai Toshiyuki
• 通讯作者: Takai Toshiyuki