Role of IgM Fc receptor in enhancing humoral immune responses and preventing autoimmunity

• Project/Area Number: 25460604
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Wang Ji-Yang 東京医科歯科大学, 難治疾患研究所, 特任講師 (80231041)
• Co-Investigator(Renkei-kenkyūsha): Ouchida Rika 東京大学, 医科学研究所, 助教 (80391887)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: IgM Fc receptor / B lymphocyte / Humoral immunity / IgM受容体 / Bリンパ球 / 液性免疫 / IgG受容体

Outline of Final Research Achievements

The following achievements were obtained: 1) The IgM Fc receptor（FcμR）physically interacts with the B cell receptor and promotes the survival and activation of antigen-stimulated B cells; 2) FcμR enhances the antibody production against foreign antigens yet suppresses autoantibody production; 3) FcμR and IgG Fc receptor (FcγR2B) compete with each other to positively and negatively regulate B cell activation; 4) FcμR is required for the normal development, maturation, activation and differentiation into antibody-producing plasma cells of the marginal zone B cells. In summary, FcμR plays a critical role in the maintenance of immune system homeostasis.

Research Products

• [Journal Article] EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity (2016)
  • Author(s): 1.Li, Y., Takahashi, Y., Fujii, S., Zhou, Y., Hong, R., Suzuki, A., Tsubata, T., Hase, K., Wang, J.-Y.
  • Journal Title: Nature Commun. Volume: 7 Issue: 1 Pages: 1-13
  • DOI: 10.1038/ncomms10836
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Expression of activation-induced cytidine deaminase is associated with a poor prognosis of diffuse large B cell lymphoma patients treated with CHOP-based chemotherapy (2016)
  • Author(s): Kawamura, K., Wada, A., Wang, J.-Y., Li, Q., Ishii, A., Tsujimura, H., Takagi, T., Itami, M., Tada, Y., Tatsumi, K., Shimada, H., Hiroshima, K. and Tagawa, M.
  • Journal Title: J. Cancer Res. Clin. Oncol. Volume: 142 Issue: 1 Pages: 27-36
  • DOI: 10.1007/s00432-015-2001-7
  • Peer Reviewed
• [Journal Article] B cells expressing CD11b effectively inhibit CD4+ T cell responses and ameliorate experimental autoimmune hepatitis (2015)
  • Author(s): Liu, X., Jiang, X., Liu, R., Wang, L., Qian, T., Zheng, Y., Deng, Y., Huang, E., Xu, F., Wang, J.-Y. and Chu, Y.
  • Journal Title: Hepatology Volume: 62 Issue: 5 Pages: 1563-1575
  • DOI: 10.1002/hep.28001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] T regulatory cells and B cells cooperate to form a regulatory loop that maintains gut homeostasis and suppresses dextran sulfate sodium-induced colitis (2015)
  • Author(s): 4.Wang, L., Ray, A., Jiang, X., Wang, J.-Y., Basu, S., Liu, X., Qian, T., He, R., Dittel, B.N. and Chu, Y.
  • Journal Title: Mucosal Immunol. Volume: 8 Issue: 6 Pages: 1297-1312
  • DOI: 10.1038/mi.2015.20
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The bullseye synapse formed between CD4+ T-cell and staphylococcal enterotoxin B-pulsed dendritic cell is a suppressive synapse in T-cell response (2015)
  • Author(s): Lin, W., Fan, Z., Suo, Y., Deng, Y., Zhang, M., Wang, J.-Y., Wei, X. and Chu, Y.
  • Journal Title: Immunol. Cell Biol. Volume: 93 Issue: 1 Pages: 99-110
  • DOI: 10.1038/icb.2014.76
  • Peer Reviewed
• [Journal Article] FcmR interacts and cooperates with the B cell receptor to promote B cell survival. (2014)
  • Author(s): Ouchida. R., Lu. Q., Liu. J., Li. Y., Chu. Y., Tsubata. T. and Wang, J.Y.
  • Journal Title: J. Immunol. Volume: 194 Issue: 7 Pages: 3096-4101
  • DOI: 10.4049/jimmunol.1402352
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Self DNA from lymphocytes that have undergone activation-induced cell death enhances murine B cell proliferation and antibody production (2014)
  • Author(s): Lu, Q., Wang, J.-Y., Wang, L., Jiang, X. and Chu, Y.
  • Journal Title: PLoS One Volume: 9 Issue: 10 Pages: e109095-e109095
  • DOI: 10.1371/journal.pone.0109095
  • Peer Reviewed / Open Access
• [Journal Article] LAPTM5 promotes lysosomal degradation of intracellular but not the cell surface CD3ζimmunol.. (2014)
  • Author(s): Kawai, Y., Ouchida, R., Yamasaki, S., Dragone, L., Tsubata, T. and Wang, J.-Y.
  • Journal Title: Cell Biol. Volume: 92 Issue: 6 Pages: 527-534
  • DOI: 10.1038/icb.2014.18
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A role for CMTM7 in BCR expression and survival in B-1a but not B-2 cells (2014)
  • Author(s): Zhang, Y., Wang, J.-Y. and Han, W.
  • Journal Title: Int. Immunol. Volume: 26 Issue: 1 Pages: 47-57
  • DOI: 10.1093/intimm/dxt042
  • Peer Reviewed
• [Journal Article] Complement-activating IgM enhances the humoral but not the T cell immune response in mice (2013)
  • Author(s): Ding, Z., Bergman, A., Rutemark, C., Ouchida, R., Ohno, H., Wang, J.-Y. and Heyman, B.
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e81299-e81299
  • DOI: 10.1371/journal.pone.0081299
  • Peer Reviewed
• [Journal Article] FcμR (Toso/Faim3) is not an inhibitor of Fas-mediated cell death in mouse T and B cells (2013)
  • Author(s): Ouchida, R., Mori, H., Ohno, H. and Wang, J.-Y.
  • Journal Title: Blood Volume: 121 Issue: 12 Pages: 2368-2370
  • DOI: 10.1182/blood-2012-12-470906
  • Peer Reviewed
• [Journal Article] High levels of AID cause strand bias of mutations at A versus T in Burkitt's lymphoma cells (2013)
  • Author(s): Kano, C. and Wang, J.-Y.
  • Journal Title: Mol. Immunol. Volume: 54 Issue: 3-4 Pages: 397-402
  • DOI: 10.1016/j.molimm.2013.01.005
  • Peer Reviewed
• [Journal Article] ADAR1 induces adenosine-targeted DNA mutations in senescent Bcl6-deficient cells (2013)
  • Author(s): Tsuruoka, N., Arima, M., Yoshida, N., Okada, S., Sakamoto, A., Hatano, M., Satake, H., Arguni, E., Wang, J.-Y., Yang, J.-H., Nishikura, K., Sekiya, S., Shozu, M. and Tokuhisa, T.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 2 Pages: 826-836
  • DOI: 10.1074/jbc.m112.365718
  • Peer Reviewed
• [Presentation] EAF2 mediates germinal center B cell apoptosis to suppress excessive humoral immune responses and prevent autoimmunity (2014)
  • Author(s): 王 継揚
  • Organizer: 2014 Chinese Society of Immunology Annual Meeting
  • Place of Presentation: Jinan, China
  • Year and Date: 2014-10-19 – 2014-10-21
  • Invited
• [Presentation] The IgM Fc receptor positively regulates B cell survival and humoral immune responses (2013)
  • Author(s): 王 継揚
  • Organizer: BcellNET Meeting
  • Place of Presentation: Uppsala, Sweden
  • Invited