Regulation of the Class Switch Recombination

• Project/Area Number: 16590226
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: SUGAI Manabu Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助手 (90303891)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: E2A / Pax5 / Id2 / Bcl6 / NFkB / IRF4 / STAT6 / NFkB / AID / STAT6 / IgE / CpG

Research Abstract

The CpG motif in DNA plays a critical role in immunity via modulating the Th1/Th2 balance. In B cells, CpG-containing oligodeoxynucleotides (CpG ODNs) inhibit IL-4-mediated class switch recombination (CSR) to IgG1 and IgE through inhibition of the germline transcription (GLT) of these isotypes. However, the molecular mechanism of this inhibitory effect remains elusive. We showed that Id2 and Bcl6, both of which inhibit IgE GLT and CSR, are not involved in this inhibitory pathway. We demonstrated that there is reduced activity of NFκB binding to the IgE promoter and a reduction of Irf4 protein in CpG ODN-treated B cells. These data indicate the critical role of NFκB and Irf4 in the regulation of IgE CSR through actions downstream of CpG signaling. Unexpectedly, STAT6 activity was not markedly changed by CpG ODN treatment. These results indicate that CpG signals work in various ways to induce Th1-skewed immune responses involving B cells.

Research Products

• [Journal Article] Enhanced anti-fibrotic activity of plasmid DNA expressing small interference RNA for TGF-beta type II receptor for a mouse model of obstructive nephropathy by cationized gelatin prepared from different amine compounds. (2006)
  • Author(s): Kushibiki T., Nagata-Nakajima N., Sugai M., Shimizu A., Tabata Y.
  • Journal Title: J Control Release. 110・3 Pages: 610-7
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Enhanced anti-fibrotic activity of plasmid DNA expressing small interference RNA for TGF-beta type II receptor for a mouse model of obstructive nephropathy by cationized gelatin prepared from different amine compounds. (2006)
  • Author(s): Kushibiki T., Nagata-Nakajima N., Sugai M., Shimizu A., Tabata Y.
  • Journal Title: J Control Release. 110(3) Pages: 610-617
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A transmembane chemokine, CXC chemokine ligand 16, expressed by lympho node fibroblastic reticular cells has the potential to regulate T cell migration and adhesion. (2006)
  • Author(s): Hara, T., Katakai, T., Lee, J.H., Nambu, Y., Nagata, N.N., Gonda, H., Sugai, M., Shimizu, A.
  • Journal Title: International Immunology 18・2 Pages: 301-311
• [Journal Article] Accessibility control of recombination at Immunoglobulin locus. (2005)
  • Author(s): Sugai M.^#, Gonda H., Nambu Y., Yokota Y., Shimizu A.
  • Journal Title: Current Immunology Reviews 1・1 Pages: 69-79
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] CpG inhibits IgE class switch recombination through suppression of NFkB activity, but not through Id2 or bc16. (2005)
  • Author(s): Sugai, M.^<#+>, Kusunoki T.^#, Gonda H., Nambu Y., Nakajima-Nagata N., Katakai T., Kusunoki M., Sakamoto A., Tokuhisa T., Nakahata T., Yokota Y., Shimizu A.
  • Journal Title: Biochem. Biophys. Res. Commun. 11・328 Pages: 499-506
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] SPINK5 polymorphism is associated with disease severity and food allergy in children with atopic dermatitis. (2005)
  • Author(s): Kusunoki T., Okafuji I., Yoshioka T., Saito M., Nishikomori R., Heike T., Sugai M., Shimizu A., Nakahata T.
  • Journal Title: J Allergy Clin Immunol. 115・3 Pages: 636-8
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Targeting of plasmid DNA to renal interstitial fibroblasts by cationized gelatin. (2005)
  • Author(s): Kushibiki T., Nagata-Nakajima N., Sugai M., Shimizu A., Tabata Y.
  • Journal Title: Biol Pharm Bull. 28・10 Pages: 2007-10
  • NAID: 110003666385
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Delivery of plasmid DNA expressing small interference RNA for TGF-beta type II receptor by cationized gelatin to prevent interstitial renal fibrosis. (2005)
  • Author(s): Kushibiki T., Nagata-Nakajima N., Sugai M., Shimizu A., Tabata Y.
  • Journal Title: J Control Release. 105・3 Pages: 318-31
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Polymorphisms in PTCH1 affect the risk of ameloblastoma. (2005)
  • Author(s): Kawabata, T., Takahashi, K., Sugai, M., Murashima, A., Ando, S., Shimizu, A., Kosugi, S., Sato, T., Nishida, M., Murakami, K., Iizuka, T.
  • Journal Title: J. Dent. Res. 84・9 Pages: 812-6
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Accessibility control of recombination at Immunoglobulin locus. (2005)
  • Author(s): Sugai M.^#, Gonda H., Nambu Y., Yokota Y., Shimizu A.
  • Journal Title: Current Immunology Reviews 1(1) Pages: 69-79
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CpG inhibits IgE class switch recombination through suppression of NFkB activity, but not through Id2 or bcl6. (2005)
  • Author(s): Sugai M.^#, Kusunoki T.^#, Gonda H., Nambu Y., Nakajima-Nagata N., Katakai T., Kusunoki M., Sakamoto A., Tokuhisa T., Nakahata T., Yokota Y., Shimizu A.
  • Journal Title: Biochem.Biophys.Res.Commun. 11(328) Pages: 499-506
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] SPINK 5 polymorphism is associated with disease severity and food allergy in children with atopic dermatitis. (2005)
  • Author(s): Kusunoki T., Okafuji I., Yoshioka T., Saito M., Nishikomori R., Heike T., Sueai M..Shimizu A., Nakahata T.
  • Journal Title: J Allergy Clin Immunol. 115(3) Pages: 636-638
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Targeting of plasmid DNA to renal interstitial fibroblasts by cationized gelatin. (2005)
  • Author(s): Kushibiki T., Nagata-Nakajima N., Sugai M., Shimizu A., Tabata Y.
  • Journal Title: Biol Pharm Bull. 28(10) Pages: 2007-2010
  • NAID: 110003666385
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Delivery of plasmid DNA expressing small interference RNA for TGF-beta type II receptor by cationized gelatin to prevent interstitial renal fibrosis. (2005)
  • Author(s): Kushibiki T., Nagata-Nakajima N., Sueai M., Shimizu A., Tabata Y.
  • Journal Title: J Control Release. 105(3) Pages: 318-331
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Polymorphisms in PTCH1 affect the risk of ameloblastoma. (2005)
  • Author(s): Kawabata, T., Takahashi, K., Sugai, M., Murashima, A., Ando, S., Shimizu, A., Kosugi, S., Sato, T., Nishida, M., Murakami, K., Iizuka, T.
  • Journal Title: J.Dent.Res. 84(9) Pages: 812-816
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Accessibility control of Recombination at Immunoglobulin Locus (2005)
  • Author(s): Sugai M., Gonda H., Nambu Y., Yokota Y., Shimizu A.
  • Journal Title: Current Immunology Reviews 1.1 Pages: 69-79
• [Journal Article] CpG inhibits IgE class switch recombination through suppression of NF kappa B activity, but not through Id2 or Bc16. (2005)
  • Author(s): Kusunoki T, Sugai M, Gonda H, Nambu Y, Nagata-Nakajima N, Katakai T, Kusunoki M
  • Journal Title: Biochem Biophys Res Commun. 11.328 Pages: 499-506
• [Journal Article] Role of Id proteins in B lymphocyte activation : new insights from knockout mouse studies. (2004)
  • Author(s): Sugai M.^#, Gonda H., Nambu Y., Yokota Y., Shimizu A.
  • Journal Title: J. Mol. Med. 82・9 Pages: 592-9
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with lymphocyte. (2004)
  • Author(s): Katakai T., Hara T., Sugai M., Gonda H., Shimizu A.
  • Journal Title: J. Exp. Med. 200 Pages: 783-795
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Roles of phospho-ERM and Rho-ROCK-signaling in lymphocyte polarity and uropod formation. (2004)
  • Author(s): Lee J-H., Katakai T., Hara T., Gonda H., Sugai M., Shimizu A.
  • Journal Title: J. Cell. Biol. 25・167 Pages: 327-37
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A novel reticular stromal structure in lymph node cortex : an immuno-platform for interactions among dendritic cells, T cells and B cells. (2004)
  • Author(s): Katakai T., Hara T., Lee J.H., Gonda H., Sugai M., Shimizu A.
  • Journal Title: Int. Immunol. 16・8 Pages: 1133-42
  • NAID: 10013425344
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] In vitro induction of adult hepatic progenitor cells into insulin-producing cells. (2004)
  • Author(s): Nakajima-Nagata N., Sakurai T., Mitaka T., Katakai T., Yamato E., Miyazaki J., Tabata Y., Sugai M., Shimizu A.
  • Journal Title: Biochem. Biophys. Res. Commun. 318 Pages: 625-30
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of Id proteins in B lymphocyte activation: new insights from knockout mouse studies. (2004)
  • Author(s): Sugai M.^#, Gonda H., Nambu Y., Yokota Y., Shimizu A.
  • Journal Title: J.Mol.Med. 82(9) Pages: 592-599
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with lymphocyte. (2004)
  • Author(s): Katakai T., Hara T., Sugai M., Gonda H., Shimizu A.
  • Journal Title: J.Exp.Med. 200 Pages: 783-795
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Roles of phospho-ERM and Rho-ROCK-signaling in lymphocyte polarity and uropod formation. (2004)
  • Author(s): Lee J-H., Katakai T., Hara T., Gonda H., Sugai M., Shimizu A.
  • Journal Title: J.Cell.Biol. 25(167) Pages: 327-337
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A novel reticular stromal structure in lymph node cortex : an immuno-platform for interactions among dendritic cells, T cells and B cells. (2004)
  • Author(s): Katakai T., Hara T., Lee J.H., Gonda H., Sugai M., Shimizu A.
  • Journal Title: Intimmunol. 16(8) Pages: 1133-1142
  • NAID: 10013425344
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] In vitro induction of adult hepatic progenitor cells into insulin-producing cells. (2004)
  • Author(s): Nakajima-Nagata N., Sakurai T., Mitaka T., Katakai T., Yamato E., Miyazaki J., Tabata Y., Sugai M., Shimizu A
  • Journal Title: Biochem.Biophys.Res.Commun. 318 Pages: 625-630
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression. (2004)
  • Author(s): Nakajima-Nagata N., Sugai M, Sakurai T., Miyazaki J., Tabata Y., Shimizu A.
  • Journal Title: Biochem.Biophys.Res.Commun. 318 Pages: 631-635
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of Id proteins in B lymphocyte activation : new insights from knockout mouse studies. (2004)
  • Author(s): Sugai M., Gonda H., Nambu Y., Yokota Y., Shimizu A.
  • Journal Title: J.Mol.Med. 82.9 Pages: 592-599
• [Journal Article] Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with lymphocytes. (2004)
  • Author(s): Katakai T., Hara T., Sugai M., Gonda H., Shimizu A.
  • Journal Title: J.Exp.Med. 200 Pages: 783-795
• [Journal Article] Roles of phospho-ERM and Rho-ROCK-signaling in lymphocyte polarity and uropod formation. (2004)
  • Author(s): Lee J-H., Katakai T., Hara T., Gonda H., Sugai M., Shimizu A.
  • Journal Title: J.Cell.Biol. 25.167 Pages: 327-337
• [Journal Article] A norvel reticular stromal structure in lymph node cortex : an immunoplatform for interaction among dendritic cells, T cells and B cells. (2004)
  • Author(s): Katakai T., Hara T., Lee J-H., Gonda H., Sugai M., Shimizu A.
  • Journal Title: Int.Immunol. 16 Pages: 1133-1142
• [Book] 免疫2005(Molecular Medicine 臨時増刊) (2004)
  • Author(s): 菅井 学, 權田 裕之, 南部 由希子, 横田 義史, 清水 章
  • Publisher: 中山書店
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Annual Review免疫2005 (2004)
  • Author(s): 南部 由希子, 菅井 学, 清水 章
  • Publisher: 中外医学社
  • Description: 「研究成果報告書概要(和文)」より