Suppression of autoimmunity by B lymphocyte membrane protein CD72

B淋巴细胞膜蛋白CD72抑制自身免疫

• 批准号: 23790531
• 负责人: WATANABE Kozo
• 金额: $ 2.83万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790531/
• 关键词: Bリンパ球; レクチン; 糖鎖

C-type lectin-like domain (CTLD) of B cell membrane protein CD72 is suggested to associated with development of autoimmune diseases. However, the glycan ligand and function of its CTLD is not clear. In this study, some kinds of sulfated glycans were identified as CD72 ligands by glycan array screening using CD72 recombinant protein.Interestingly, some of the identified CD72 ligands are autoimmune disease-associated antigens. In addition, the effect of CD72 ligand on B cell antigen receptor (BCR) signaling in primary B cells from QM mice and QM CD72 deficient mice by analyzing calcium influx using NP-conjugated CD72 ligand and NP-conjugated BSA, showed CD72-dependent reduction of BCR signaling following ligation of CD72 ligand-containing antigen. Moreover, the amount of serum anti-CD72 ligand IgM classantibody was increased in C57BL/6 CD72 deficient mice compared with that in C57BL/6 mice. These results suggest novel self and non-self recognition mechanism of B cells by CD72-CD72 ligand interaction-mediated suppression of BCR signaling and antibody production against CD72 ligand-containing antigens.

B 细胞膜蛋白 CD72 的 C 型凝集素样结构域 (CTLD) 被认为与自身免疫性疾病的发生有关。然而，其CTLD的聚糖配体及其功能尚不清楚。本研究利用CD72重组蛋白通过聚糖阵列筛选，鉴定出一些硫酸化聚糖为CD72配体。有趣的是，一些鉴定出的CD72配体是自身免疫性疾病相关抗原。此外，通过使用 NP 缀合的 CD72 配体和 NP 缀合的 BSA 分析钙流入，CD72 配体对 QM 小鼠和 QM CD72 缺陷小鼠的原代 B 细胞中 B 细胞抗原受体 (BCR) 信号传导的影响显示，在连接含 CD72 配体的抗原后，BCR 信号传导出现 CD72 依赖性减少。此外，与C57BL/6小鼠相比，C57BL/6 CD72缺陷小鼠的血清抗CD72配体IgM类抗体的量增加。这些结果表明，B 细胞通过 CD72-CD72 配体相互作用介导的 BCR 信号传导抑制和针对含 CD72 配体的抗原的抗体产生来实现新的自我和非自我识别机制。

项目成果

CD22-antagonists with nanomolar potency: the synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold.

• DOI: 10.1016/j.bmc.2011.01.060
• 发表时间: 2011-03-15
• 期刊: BIOORGANIC & MEDICINAL CHEMISTRY
• 影响因子: 3.5
• 作者: Abdu-Allah, Hajjaj H. M.;Watanabe, Kozo;Completo, Gladys C.;Sadagopan, Magesh;Hayashizaki, Koji;Takaku, Chiaki;Tamanaka, Taichi;Takematsu, Hiromu;Kozutsumi, Yasunori;Paulson, James C.;Tsubata, Takeshi;Ando, Hiromune;Ishida, Hideharu;Kiso, Makoto
• 通讯作者: Kiso, Makoto

The use of cationic nanogels to deliver proteins to myeloma cells and primary T lymphocytes that poorly express heparan sulfate.

• DOI: 10.1016/j.biomaterials.2011.04.058
• 发表时间: 2011-09
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Kozo Watanabe;Yumiko Tsuchiya;Y. Kawaguchi;S. Sawada;Hirohito Ayame;K. Akiyoshi;T. Tsubata

Design and synthesis of multivalent heterobifunctional CD22-ligand as a potential immunomodulator.

设计和合成多价异双功能 CD22 配体作为潜在的免疫调节剂。

• 发表时间: 2011
• 期刊: Synthesis.
• 作者: Abdu-Allah;H. H. M.;Watanabe;K.;Kanie;O.;Tsubata;T. Ishida;H. and Kiso;M.
• 通讯作者: M.