Suppression of autoimmunity by B lymphocyte membrane protein CD72

• Project/Area Number: 23790531
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: WATANABE Kozo 東京医科歯科大学, 難治疾患研究所, 助教 (20376718)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: Bリンパ球 / レクチン / 糖鎖

Research Abstract

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.

Research Products

• [Journal Article] The use of cationic nanogels to deliver proteins to myeloma cells and primary T lymphocytes that poorly express heparan sulfate. (2011)
  • Author(s): Watanabe, K., Tsuchiya, Y., Kawaguchi, Y., Sawada, S., Ayame, H., Akiyoshi, K. and Tsubata, T.
  • Journal Title: Biomaterials. Volume: 32 Pages: 5900-5905
  • Peer Reviewed
• [Journal Article] CD22-antagonists with nanomolar potency: The synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold. (2011)
  • Author(s): Abdu-Allah, H. H. M., Watanabe, K., Completo, G. C., Sadagopan, M., Hayashizaki, K., Takaku, C., Tamanaka, T., Takematsu, H., Kozutsumi, Y., Paulson, J.C., Tsubata, T., Ando, H., Ishida, H. and Kiso, M.
  • Journal Title: Bioorg. Med. Chem. Volume: 19 Pages: 1966-1971
  • Peer Reviewed
• [Journal Article] Design and synthesis of multivalent heterobifunctional CD22-ligand as a potential immunomodulator. (2011)
  • Author(s): Abdu-Allah, H. H. M., Watanabe, K., Kanie, O., Tsubata, T. Ishida, H. and Kiso, M.
  • Journal Title: Synthesis. Volume: 18 Pages: 2968-2974
  • Peer Reviewed
• [Journal Article] Cationic nanogels efficiently deliver proteins to myeloma cells and primary T lymphocytes poorly expressing heparan sulfate (2011)
  • Author(s): K.Watanabe, et al
  • Journal Title: Biomaterials Volume: 32 Issue: 25 Pages: 5900-5905
  • DOI: 10.1016/j.biomaterials.2011.04.058
  • Peer Reviewed
• [Journal Article] CD22-Antagonists with nanomolar potency : The synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold (2011)
  • Author(s): Abdu-Allah, H.H.M., Watanabe, K., Completo, G.C., Sadagopan, M., Hayashizaki, K., Takaku, C., Tamanaka, T., Takematsu, H., Kozutsumi, Y., Paulson, J.C., Tsubata, T., Ando, H., Ishida, H., Kiso, M.
  • Journal Title: Bioorg.Med.Chem Volume: 19 Issue: 6 Pages: 1966-1971
  • DOI: 10.1016/j.bmc.2011.01.060
  • Peer Reviewed
• [Journal Article] Design and synthesis of a multivalent heterobifunctional CD22 ligand as apotential immunomodulator (2011)
  • Author(s): Abdu-Allah, H.H.M., Watanabe, K., Daikoku, S., Kanie, O., Tsubata, T., Ando, H., Ishida, H., Kiso, M.
  • Journal Title: Synthesis Volume: 18 Issue: 18 Pages: 2968-2974
  • DOI: 10.1055/s-0030-1260151
  • Peer Reviewed