Molecular base of the defenses against infection by IgM and IgA

• Project/Area Number: 16017215
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: University of Tsukuba
• Principal Investigator: SHIBUYA Akira University of Tsukuba, Professor, 人間総合科学研究科, 教授 (80216027)
• Co-Investigator(Kenkyū-buntansha): HONDA shin-ichiro University of Tsukuba, Lecturer, 人間総合科学研究科, 講師 (60360640)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥15,000,000 (Direct Cost: ¥15,000,000); Fiscal Year 2005: ¥7,500,000 (Direct Cost: ¥7,500,000); Fiscal Year 2004: ¥7,500,000 (Direct Cost: ¥7,500,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Journal Article] A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory. (2006)
  • Author(s): Murayama A et al.
  • Journal Title: Embo Journal 25 Pages: 1081-92
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Tumor rejection by the polivirus receptor family ligands of the DNAM-1(CD226) receptor. (2006)
  • Author(s): Tahara-Hanaoka S et al.
  • Journal Title: Blood 107 Pages: 1491-1796
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Critical role of M. tuberculosis for dendritic cell maturation to induce collagen-induced arthritis in H-2b background of C57BL/6 mice. (2006)
  • Author(s): Kai H, Shibuya K, Wang Y, Kameta H, Kameyama T, Tahara-Hanaoka S, Miyamoto A, Honda S, Matsumoto I, Koyama A, Sumida T, Shibuva A.
  • Journal Title: Immunology. 118 Pages: 233-239
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A specific CpG demethylation in the human IL-2 gene promoter as an epigenetic memory. (2006)
  • Author(s): Murayama A, Sakura K, Nakayama M, Yasuzawa K, Fujita E, Wang Y, Ushijima T, Shibuya K, Shibuya A, Kawabe Y, Yanagisawa J.
  • Journal Title: EMBO J 25 Pages: 1081-92
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Shibuya A Tumor rejection by the poliovirus receptor family ligands of the DNAM-1(CD226) receptor. (2006)
  • Author(s): Tahara-Hanaoka S, Shibuya K, Kai H, Miyamoto A, Morikawa Y, Ohkochi N, Honda SI
  • Journal Title: Blood 107 Pages: 1491-1496
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Critical role of M. tuberculosis for dendritic cell maturation to induce collagen-induced arthritis in H-2b background of C57BL/6 mice. (2006)
  • Author(s): Kai H et al.
  • Journal Title: Immunology (In press)
• [Journal Article] Tumor rejection by the poliovirus receptor family ligands of the DNAM-1(CD226) receptor. (2006)
  • Author(s): Tahara-Hanaoka S et al.
  • Journal Title: Blood 107 Pages: 1491-1796
• [Journal Article] Critical role of M.tuberculosis for dendritic cell maturation to induce collagen-induced arthritis in H-2b background of C57BL/6 mice. (2005)
  • Author(s): Kai H et al.
  • Journal Title: Immunology (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification and characterrization of murine DNAM-1(CD226) and its poliovirus receptor family ligands. (2005)
  • Author(s): Tahara-Hanaoka S et al.
  • Journal Title: Biochem Biophys Res Commun 329 Pages: 996-1000
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Requirement of the serine at residue 329 for lipid raft recruitment of DNAM-1(CD226). (2005)
  • Author(s): Shirakawa J et al.
  • Journal Title: International Immunology 17 Pages: 217-223
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] DNAM-1(CD226),a two-sword fencer for innate and adaptive immunity. (2005)
  • Author(s): Shibuya A et al.
  • Journal Title: Curr Med Chem-AIAA 4 Pages: 53-58
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Requirement of the tyrosines at residues 258 and 270 of MAIR-I in inhibitory effect on degranulation from basophic leukemia RBL-2H3. (2005)
  • Author(s): Okoshi Y et al.
  • Journal Title: International Immunology 17 Pages: 65-72
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Positinal indentification of an asthma susceptibility gene on human chromosome 5q33. (2005)
  • Author(s): Noguchi E et al.
  • Journal Title: Am J Respir Crit Care Med 172 Pages: 183-188
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Suppression of eosinophilic airway inflammation by treatment with alpha-galactosylceramide. (2005)
  • Author(s): Morishima Y et al.
  • Journal Title: Eur J Immunol 35 Pages: 2803-2814
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Requirement of the serine at residue 329 for lipid raft recruitment of DNAM-1 (CD226). (2005)
  • Author(s): Shirakawa J, Shibuya K, Shibuya A.
  • Journal Title: Int Immunol. 17 Pages: 217-223
  • NAID: 10015452215
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] DNAM-1(CD226), a two-sword fencer for innate and adaptive immunity. (2005)
  • Author(s): Shibuva A, Tahara-Hanaoka S, Shibuya K.
  • Journal Title: Curr Med Chem-AIAA. 4 Pages: 53-58
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Requirement of the tyrosines at residues 258 and 270 of MAIR-I in inhibitory effect on degranulation from basophilic leukemia RBL-2H3. (2005)
  • Author(s): Okoshi Y, Tahara-Hanaoka S, Nakahashi C, Honda S, Miyamoto A, Kojima H, Nagasawa T, Shibuya K, Shibuya A
  • Journal Title: Int Immunol. 17 Pages: 65-72
  • NAID: 10014258578
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Positional identification of an asthma susceptibility gene on human chromosome 5q33 (2005)
  • Author(s): Noguchi, E., Yokouchi, Y., Zhang, J., Shibuya, K., Shibuya, A., Bannai, M., Tokunaga, K., Doi, H., Tamari, M., Shimizu, M., Shirakawa, T., Shibasaki, M., Ichikawa, K., Arinami, T.
  • Journal Title: Am J Respir Crit Care Med 172 Pages: 183-8
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Suppression of eosinophilic airway inflammation by treatment with alpha-galactosylceramide (2005)
  • Author(s): Morishima, Y., Ishii, Y., Kimura, T., Shibuya, A., Shibuya, K, Hegab, A.K, Iizuka, T., Kiwamoto, T., Matsuno, Y., Sakamoto, T., Nomura, A., Taniguchi, M., Sekizawa, K.
  • Journal Title: Eur J Immunol 35 Pages: 2803-2814
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification and characterization of murine DNAM-1 (CD226) and its poliovirus receptor family ligands. (2005)
  • Author(s): Tahara-Hanaoka S et al.
  • Journal Title: Biochem Biophys Res Commun 329 Pages: 996-1000
• [Journal Article] DNAM-1(CD226), a two-sword fencer for innate and adaptive immunity. (2005)
  • Author(s): Shibuya A et al.
  • Journal Title: Curr Med Chem-AIAA 4 Pages: 53-58
• [Journal Article] Requirement of the tyrosines at residues 258 and 270 of MAIR-1 in inhibitory effect on degranulation from basophilic leukemia RBL-2H3. (2005)
  • Author(s): Okoshi Y et al.
  • Journal Title: International Immunology 17 Pages: 65-72
• [Journal Article] Positional identification of an asthma susceptibility gene on human chromosome 5q33. (2005)
  • Author(s): Noguchi E et al.
  • Journal Title: Am J Respir Crit Care Med 172 Pages: 183-188
• [Journal Article] Suppression of eosinophilic airway inflammation by treatment with alpha- galactosylceramide. (2005)
  • Author(s): Morishima Y et al.
  • Journal Title: Eur J Immunol 35 Pages: 2803-2814
• [Journal Article] Requirement of the serine at residue 329 for lipid raft recruitment of DNAM-1 (CD226) (2005)
  • Author(s): Shirakawa J, Shibuya K, Shibuya, A.
  • Journal Title: Int Immunol 17 Pages: 217-223
  • NAID: 10015452215
• [Journal Article] Requirement of the tyrosines at residues 258 and 270 of MAIR-I in inhibitory effect on degranulation from basophilic leukemia RBL-2H3 (2005)
  • Author(s): Okoshi Y, et al.
  • Journal Title: Int Immunol 17 Pages: 65-72
• [Journal Article] DNAM-1(CD226), a two-sword fencer for innate and adaptive immunity. (2004)
  • Author(s): Shibuya A, Tahara-Hanaoka S, Shibuya K.
  • Journal Title: Curr Med Chem-AIAA 4 Pages: 53-58
• [Journal Article] Successful gene transfer into human CD4 positive T cells mediated by lentiviral vectors. (2004)
  • Author(s): Shibuya K, et al.
  • Journal Title: Immunology 12 Pages: 91-92
• [Journal Article] Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112) (2004)
  • Author(s): Tahara-Hanaoka S, et al.
  • Journal Title: Int Immunol 16 Pages: 533-538
• [Journal Article] Treatment with alpha-galactosylceramide attenuates the development of bleomycin-induced pulmonary fibrosis (2004)
  • Author(s): Kimura T, et al.
  • Journal Title: J Immunol 172 Pages: 5782-5789