Elucidation of the mechanism on carbohydrate antigen recognition by B cells through CD1d mediated signaling and establishment of a method to regulate B cells responding to the carbohydrate antigens in ABO-incompatible transplantation and xe

阐明 B 细胞通过 CD1d 介导的信号识别碳水化合物抗原的机制，并建立在 ABO 不相容移植和 xe 中调节 B 细胞对碳水化合物抗原反应的方法

基本信息

批准号：
18390349
负责人：
ASAHARA Toshimasa
金额：
$ 11.21万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

In ABO-blood group incompatible transplantation and xenotransplantation, grafted organs will be rejected because antibody (Ab)-mediated rejection is induced in responses to blood group A/B antigens, Gal α 1-3Galb1-4GlcNAc (Gal) or N-glycolylneuraminic acid (NeuGc) carbohydrates, which are widely expressed on the organ vessel epithelia. We have attempted to establish a specific immunosuppressive method targeting B cells responding to A/B, Gal and NeuGc carbohydrate antigens.In this study, we have analyzed the role of natural killer T (NKT) cells in the differentiation of B cells responding to the transplant-related carbohydrates. In the wild-type (WT) control mice, anti-A IgM/IgG Ab production occurred and was accelerated after the immunization with human red blood cells (RBCs) and α Galactosylceramide ( α GalCer) (an unique carbohydrate antigen that is presented on CD1d molecules and activates NKT cells). On the other hand, in the CD1d (ligand to the V α 14 T cell receptors used predominantly in NKT cells) knockout (KO) mice, anti-A IgM production was significantly reduced and anti-A IgG-class switching could not be observed. There was no difference in anti-allogeneic MHC Ab production between WT and CD1dKO mice, and IgG-class switching could be normally observed in both background mice. Based on these findings, it is likely that the suppressive modulation of CD1d molecule-mediated signaling between NKT cells and B cells might lead to the avoidance of Ab-mediated rejection in ABO-incompatible transplantation, whereas this strategy could not prevent Ab production from B cells responding to allogeneic MHC antigens. In order to investigate further such roles of NKT cells in the differentiation of B cells responding to the xenogeneic carbohydrate antigens, we have now established Gal/CD1d double KO mice and NeuGc/CD1d double KO mice by mating either Gal KO or NeuGc KO mice with CD1dKO mice.

在Abo-Blood群体的无效和异种移植中，由于对血液组A/B抗原的反应诱导的抗体（AB），GALα1-3GALB1-4GLCNAC（GAL）或N-糖苷甲基尿素酸（Neugc）碳酸（neugc）碳酸盐（Neugc）碳纤维（neugc）carbohydrates，抗体（AB）会被拒绝。这是广泛表达的器官容器上皮。相关的碳水化合物发生。（在NKT细胞中使用的Vα14T细胞受体的配体）小鼠，抗A IgM的产生是显着红色的，并且在抗合并MHC AB之间的NCE中无法观察到抗A IgGG级切换。 CD1DKO小鼠和IgG级切换通常在两种背景小鼠中都可以观察到。抗原在B细胞的分化中，对异构碳水化合物抗原和Neugc/CD1D双KO小鼠响应，通过将gal ko或neugc ko小鼠与CD1DKO小鼠配对。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Elucidation of the mehcanism of differentiation of B cells responding to blood group antigen and application to ABO-incompatible renal transplantation

阐明B细胞响应血型抗原的分化机制及其在ABO血型不合肾移植中的应用

DOI：
发表时间：
2008
期刊：
影响因子：
0
作者：
T.;Irei;H.;Ohdan;Y.;Igarashi;K.;Ishiyama;Y.;Tanaka;K.;Ide;M.;Shishida;M.;Ohira;H.;Tahara;M.;Bansyodani;Y.;Fudaba;F.;Shintaku;T.;Ishikawa;Y.;Fukuda;T.;Asahara
通讯作者：
Asahara

Role for CD47-SIRPalpha signaling in xenograft rejection by macrojthages

CD47-SIRPα信号在巨噬细胞异种移植排斥中的作用

DOI：
发表时间：
2007
期刊：
Proc Natl Acad Sci USA 104(12)
影响因子：
0
作者：
Ide;Kentaro;Hui;Wang;Tahara;Hiroyuki;Jianxiang;Liu;Xiaoying;Wang;Asahara;Toshimasa;Megan;Sykes;Yong-Guang;Yang;Ohdan;Hideki;Fuchimoto;Yasushi;Egawa;Hiroto;Asahara;Toshimasa
通讯作者：
Toshimasa

CD47-SIRPαシグナル制御によるマクロファージ性拒絶反応回避のメカニズム

CD47-SIRPα信号控制逃避巨噬细胞排斥的机制