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.

免疫球蛋白通过启动经典的补体级联反应在先天免疫中发挥关键作用。最近，一种新的免疫球蛋白和免疫球蛋白A的Fc受体Fcα/μR终于被克隆，但其在免疫球蛋白M介导的免疫中的作用尚不清楚。在此，我们发现，在Fcα/μR缺陷小鼠中，边缘带B细胞和滤泡树突状细胞优先表达Fcα/μR，尽管抗TD抗原的GC形成正常，但抗TI抗原的GC形成增强，B细胞和滤泡树突状细胞都参与其中。抗原-Ig M复合体的形成通过Ig M-Fcα/μR相互作用减少了bcr介导的B细胞活化和补体依赖性抗原沉积。Fcα/μR基因缺陷小鼠对TI抗原的反应表现为MZB细胞和FDC的抗原滞留增强，淋巴器官表达CXCL13。此外，在Fcα/μR缺陷小鼠中，TI抗原诱导的GC的形成导致了IgG3的亲和力成熟。取消补体途径可完全减弱这些表型。综上所述，Fcα/μR可能通过与补体级联反应，对免疫球蛋白M介导的针对TI抗原的免疫应答发挥微调作用。

项目成果

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-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.

Treatment with alpha-galactosylceramide attenuates the development of bleomycin-induced pulmonary fibrosis.

• 发表时间: 2004
• 期刊: Journal of immunology
• 影响因子: 4.4
• 作者: Toru Kimura;Yukio Ishii;Y. Morishima;A. Shibuya;K. Shibuya;M. Taniguchi;M. Mochizuki;A. Hegab;T. Sakamoto;A. Nomura;K. Sekizawa

Critical role of M-tuberculosis for dendritic cell maturation to induce collagen-induced arthritis in H-2b background of C57BL/6 mice

• DOI: 10.1111/j.1365-2567.2006.02361.x
• 发表时间: 2006-06-01
• 期刊: IMMUNOLOGY
• 影响因子: 6.4
• 作者: Kai, Hirayasu;Shibuya, Kazuko;Shibuya, Akira
• 通讯作者: Shibuya, Akira

DNAM-1 (CD226): A two-sword fencer for innate and adaptive immunity

• DOI: 10.2174/1568014053005390
• 发表时间: 2005-02-01
• 期刊: Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents
• 作者: Shibuya, Akira;Tahara-Hanaoka, Satoko;Shibuya, Kazuko
• 通讯作者: Shibuya, Kazuko