Molecular base of the defenses against infection by IgM and IgA

IgM 和 IgA 感染防御的分子基础

• 批准号: 16017215
• 负责人: SHIBUYA Akira
• 金额: $ 9.6万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16017215/
• 关键词: IgM; IgA Fccdat; Fcα; μR; Marginal zone B cell; follicular dendritic cell; CXCL13; Fc(alpha); (mu)receptor; 液性免疫; 抗体; 自然免疫; 獲得免疫; 感染症

IgM plays pivotal role in innate immunity by initiating classical complement cascade. Recently, an novel Fc receptor for IgM and IgA, Fcα/μR, was finaly cloned, but its involvement in IgM-mediated immunity was unclear. Here, we show that marginal zone B (MZB) cells and follicular dendritic cells (FDC) preferentially express Fcα/μR. In Fcα/μR-deficient mice, although GC formation against TD antigen was normal, that against TI antigen was enhanced, in which both B cells and FDC were involved. Formation of antigen-IgM complex decreased BCR-mediated activation and complement dependent antigen deposition of B cells via IgM-Fcα/μR interaction. Fcα/μR-deficient mice showed enhanced antigen retention by MZB cells and FDC, and CXCL13 expression in lymphoid organ in response to TI antigen. Moreover, TI antigen induced GC formation in Fcα/μR-deficient mice result in the affinity maturation of IgG3. Abrogation of complement pathway completely attenuated these phenotypes. Collectively, Fcα/μR may exert fine-tuning mechanism of IgM-mediated immune responses against TI antigens by interacting with the complement cascades.

IgM 通过启动经典补体级联在先天免疫中发挥关键作用，最近，IgM 和 IgA 的新型 Fc 受体 Fcα/μR 最终被克隆，但其在 IgM 介导的免疫中的作用尚不清楚。在 Fcα/μR 缺陷小鼠中，B (MZB) 细胞和滤泡树突状细胞 (FDC) 优先表达 Fcα/μR，尽管 GC 的形成会阻碍 Fcα/μR 的形成。 TD抗原正常，针对TI抗原的抗原增强，其中B细胞和FDC均参与其中，抗原-IgM复合物的形成通过IgM-Fcα/μR相互作用减少了BCR介导的激活和补体依赖性抗原沉积。 /μR缺陷小鼠表现出MZB细胞和FDC增强的抗原保留，以及淋巴器官中响应TI抗原的CXCL13表达，此外，TI抗原诱导GC形成。 Fcα/μR 缺陷小鼠导致 IgG3 的亲和力成熟，从而完全减弱了这些表型。总的来说，Fcα/μR 可能通过与补体级联相互作用发挥 IgM 介导的针对 TI 抗原的免疫反应的微调机制。

项目成果

Requirement of the tyrosines at residues 258 and 270 of MAIR-I in inhibitory effect on degranulation from basophic leukemia RBL-2H3.

MAIR-1的残基258和270处的酪氨酸对碱性白血病RBL-2H3脱粒的抑制作用的需要。

• 发表时间: 2005
• 期刊: International Immunology 17
• 作者: Wachino J;Yamane K;Shibayama K;Kurokawa H;Shibata N;Suzuki S;Doi Y;Kimura K;Ike Y;Arakawa Y;Okoshi Y et al.
• 通讯作者: Okoshi Y et al.

Successful gene transfer into human CD4 positive T cells mediated by lentiviral vectors.

由慢病毒载体介导成功地将基因转移到人类 CD4 阳性 T 细胞中。

• 发表时间: 2004
• 期刊: Immunology 12
• 作者: Shibuya K;et al.
• 通讯作者: et al.

Requirement of the tyrosines at residues 258 and 270 of MAIR-1 in inhibitory effect on degranulation from basophilic leukemia RBL-2H3.

MAIR-1 残基 258 和 270 处的酪氨酸对嗜碱性白血病 RBL-2H3 脱粒的抑制作用的需要。

• 发表时间: 2005
• 期刊: International Immunology 17
• 作者: Suto A;Nakajima H;Takatori H;Tokumasa N;Suzuki K;Iwamoto I;Shirakawa J et al.;Shibuya A et al.;Okoshi Y et al.
• 通讯作者: Okoshi Y et al.

Positional identification of an asthma susceptibility gene on human chromosome 5q33.

• DOI: 10.1164/rccm.200409-1223oc
• 发表时间: 2005-07
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7
• 作者: E. Noguchi;Y. Yokouchi;Jiang Zhang;K. Shibuya;A. Shibuya;M. Bannai;K. Tokunaga;Hitomi Doi;M. Tamari;M. Shimizu;T. Shirakawa;M. Shibasaki;K. Ichikawa;T. Arinami

Positinal indentification of an asthma susceptibility gene on human chromosome 5q33.

人类染色体 5q33 上哮喘易感基因的位置鉴定。

• 发表时间: 2005
• 期刊: Am J Respir Crit Care Med 172
• 作者: 東倉洋一;岡村久道;高村信;岡田仁志;曽根原登;Tahara-Hanaoka S et al.;Noguchi E et al.
• 通讯作者: Noguchi E et al.