最近の業績 

Klionsky, D.J., Abdalla, F. C. Tsubata, T. et al. (2012): Guidelines for the use and
 interpretation of assays for monitoring autophagy. Autophagy 8: 1-100.

Kishi, Y., Higuchi, T., Phoon, S., Kamiya, K., Riemekasten, G., Akiyoshi, K., Weigert, M. 
and Tsubata, T. (2012): Apoptotic marginal zone deletion of anti-Sm/ribonucleoprotein 
B cells. Proc. Natl. Acad. Sci. USA. 109(20) : 7811-6

Tsubata T.(2012): Role Of Inhibitory Bcr Co-Receptors In Immunity. Infect Disord
 Drug Targets. Mar 6.

Tsubata, T. (2011): ЯПОНИЯ ПОСЛЕ ЗЕМЛЕТРЯСЕНИЯ, ЦУНАМИ И
 КАТАСТРОФЫ В ФУКУСИМЕ. РОССИЯ И ГЕРМАНИЯ 2:30-31.

Megesh, S., Ando, H., Tsubata, T., Ishida, H., Kiso, M. (2011) High-Affinity Ligands of 
Siglec Receptors and their Therapeutic Potentials. Current Medicinal Chemistry 18:
3537-3550

Poe, J. C., Smith , S. H., Haas, K. M., Yanabe, K., Tsubata, T., Matsushita, T. and 
Tedder, T. F. (2011) Amplified B lymphocyte CD40 signaling drives regulatory B10 cell 
expansion in mice. PLoS ONE 6: 22464

Tsubata, T. (2011) Role of inhibitory BCR co-receptors in immunity. Infectious 
Disorders - Drug Targets (in press).

Abdu-Allah, H. H. M, Watanabe, K., Kanie, O., Tsubata, T. Ishida, H. and Kiso, M.
(2011). Design and synthesis of multivalent heterobifunctional CD22-ligand as a 
potential immunomodulator. Synthesis (in press).


Watanabe, K., Tsuchiya, Y., Kawaguchi, Y., Sawada, S.-i., Ayame, H., Akiyoshi, K. and
 Tsubata, T. (2011): The use of cationic nanogels to deliver proteins to myeloma cells 
and primary T lymphocytes that poorly express heparan sulfate. Biomaterials. 32: 5900
-5905.

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. (2011): CD22-antagonists with nanomolar potency: 
The synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold. 
Bioorg. Med. Chem. 19: 1966-1971.

Bolduc, A., Long, E., Stapler, D., Cascalho, M., Tsubata, T. Koni, P. A. and Shimoda, 
M. (2010): Constitutive CD40L expression on B cells prematurely terminates germinal 
center response and leads to augmented plasma cell production in T cell areas. J. 
Immunol. 185: 220-230.

Kishi, Y., Aiba, Y., Higuchi, T., Furukawa, K., Tokuhisa, T., Takemori, T. and Tsubata, T. 
(2010): Augmented antibody response with premature germinal center regression in 
CD40L-transgenic mice. J. Immunol. 185: 211-219.

Ishiura, N., Nakashima, H., Watanabe, R., Kuwano, Y., Adachi, T., Takahashi, Y., 
Tsubata, T., Okochi, H., Tamaki, K., Tedder, TF., Fujimoto M.(2010): Differential 
phosphorylation of functional tyrosines in CD19 modulates B lymphocyte activation. 
Eur J Immunol. 40: 1192-1204.

Man, R.-Y., Onodera, T., Komatsu, E., Tsubata, T. (2010): Augmented B lymphocyte 
response to antigen in the absence of antigen-induced B lymphocyte signaling in an 
IgG-transgenic mouse line. Plos one. 5:8815.

 Abdu-Allah, H. H. M., Watanabe, K., Hayashizaki, K., Takaku, C., Tamanaka, T., 
Takematsu, H., Kozutsumi, Y., Tsubata, T., Ishida, H. and Kiso, M. (2009): Potent small 
molecule mouse CD22 inhibitors: exploring the interaction of the residue at C-2 of 
sialic acid scaffold. Bioorg. Med. Chem. Lett. 19:5573-75.
        
Abdu-Allah, H. H. M., Watanabe, K., Hayashizaki, K., Iwayama, Y., Takematsu, H.,
Kozutsumi, Y., Tsubata, T., Ishida, H. and Kiso, M (2009): Synthesis of biotinylated 
sialoside to probe CD22-ligand interactions. Tetrahedron Lett. 50:4488−91.
        
 Engels, N., Konig, L. M., Heemann, C., Lutz, J., Tsubata, T., Griep, S. and Wienands, 
J. (2009): The immunoglobulin tail tyrosine of surface IgG and IgE provides antigen 
receptor-intrinsic costimulation to class-switched B cells. Nature Immunol. 
        
Yanaba, K., Bouaziz, J.-D., Matsushita, T., Tsubata, T., and Tedder, T. F. (2009): The 
development and function of regulatory B cells expressing IL-10 requires antigen 
receptor diversity and TLR signals. J. Immunol. 182:7459-72.
        
Watanabe, K and Tsubata, T. (2009): Autophagy connects antigen receptor signaling 
to costimulatory signaling in B lymphocytes. Autophagy.5: 108-110.

Toda, M., Hisano, R., Yurugi, H., Akita, K., Maruyama, K., Inoue, M., Adachi, T., 
Tsubata, T. and Nakada, H. (2009): Ligation of tumor-produced mucins to CD22
 dramatically impairs splenic marginal zone B cells. Biochem J. 417:673-683.

Hou, R., Ohtsuji, M., Ohtsuji, N., Zhang, L., Adachi, T., Hirose, S. and Tsubata, T.
 (2009): The centromeric interval of chromosome 4 derived from C57BL/6 mice 
accelerates type 1 diabetes in NOD.CD72b congenic mice. Biochem. Biophys. Res. 
Comm. 380: 193-197.

Yan, B.-C., Adachi, T. and Tsubata, T.(2008): ER stress is involved in B cell antigen 
receptor ligation-induced apoptosis. Biochem. Biophys. Res. Comm. 365:143-148.

Onodera, T., Poe, J. C., Tedder, T. F. and Tsubata, T. (2008): CD22 regulates time
 course of both B cell division and antibody response. J. Immunol. 180: 907-913.

Zhu, C., Fujimoto, M., Sato, M., Yanagisawa, T. and Tsubata, T. (2008): Novel binding 
site for SH2-containing protein tyrosine phosphatase-1 in CD22 activated by B
 Lymphocyte stimulation with antigen. J. Biol. Chem. 283: 1653-1659.

Watanabe, K., Ichinose, S., Hayashizaki, K. and Tsubata, T. (2008): Induction of 
autophagy by B cell antigen receptor stimulation and its inhibition by costimulation. 
Biochem. Biophys. Res. Comm. 374:274-281

Abdu-Allah, H. H. M., Tamanaka, T., Yu, J., Lu, Z., Sadagopan, M., Adachi. T., 
Tsubata, T., Kelm, S., Ishida, H. and Kiso, M. (2008): Design, synthesis, and structure-
activity relationships of novel series of sialosides as CD22-specific inhibitors. J. 
Medicinal Chem. 51: 6665-6681.

Tsubata, T. (2008): Siglec-2 is a key molecule for immune response. Experimental 
Glycoscience, Glycobiology. Springer. p.167-170.

Adachi, T., Tsubata, T., (2008): FRET-based Ca2+ measurement in B lymphocyte by
 flow cytometry and confocal microscopy. Biochem Biophys Res Commun. 367:377-82

Watanabe, K and Tsubata, T. (2008): Autophagy connects antigen receptor signaling 
to costimulatory signaling in B lymphocytes. Autophagy. 

Sato, M., Adachi, T. and Tsubata, T. (2007): Augmentation of signaling through BCR 
containing IgE but not that containing IgA due to lack of CD22-mediated signal 
regulation. J. Immunol. 178: 2901-2907. 

Yu, J., Sawada, T., Adachi, T., Gao, X., Takematsu, H., Kozutsumi, Y., Ishida, H., Kiso, 
M. and Tsubata, T. (2007): Synthetic glycan ligand excludes CD22 from antigen 
receptor-containing lipid rafts. Biochem. Biophys. Res. Comm. 360: 759-764

Adachi, T., Wienands, J., Tsubata, T. and Kurosaki, T. (2007): Interdomain A is 
crucial for ITAM-dependent and -independent regulation of Syk. Biochem. Biophys.
 Res. Comm. 364: 111-7

Devi, S. S., Hagiyama, H., Adachi, T., Miyasaka, N. and Tsubata, T. (2006): The tumor 
suppressor p53 is not required for antigen receptor-mediated apoptosis of B 
lymphocytes. Signal Transduction 6: 54-61.

Akagawa, M., Ito, S., Toyoda, K., Ishii, Y., Tatsuda, E., Shibata, T., Kawai, Y., Ishino, K., 
Kishi, Y., Adachi, T., Tsubata, T., Takasaki, Y., Hattori, N., Matsuda, T. and Uchida, K. 
(2006): Bispecific antibodies against modified protein and DNA with oxidized lipids. 
Proc. Natl. Acad. Sci. USA. 103: 6160-5. 

Tsubata, T. (2006): B cell abnormality and systemic lupus erythematosus. APLAR 
J. Rheum. 9: 372-376

Tsubata, T. (2005): B cell abnormality and autoimmune disorders. Autoimmunity 38: 
331-337.

Hirai, H., Adachi, T., and Tsubata, T. (2004): Involvement of cell cycle progression in 
survival signaling through CD40 in B lymphocyte line WEHI-231. Cell Death Differ. 11: 
261-269.

Kawamura, T., Kanai, T., Dohi, T., Uraushihara, K., Totsuka, T., Iiyama, R., Taneda, C., 
Yamazaki, M., Nakamura, T., Higuchi, T., Aiba, Y., Tsubata, T. and Watanabe, M. (2004):
Ectopic CD40 ligand expression on B cells trigger intestinal inflammation. J. Immunol. 
172: 6388-6397.

Nitschke, L. and Tsubata, T. (2004): Molecular interactions regulate BCR signal 
inhibition by CD22 and CD72. Trends Immunol. 25: 543-550.

Suzuki, A, Kaisho, T., Ohishi, M., Tsukio-Yamaguchi, M., Tsubata, T., Koni, P. A., 
Sasaki, T., Mak, T. W., and Nakano, T. (2003): Critical roles of Pten in B cell 
homeostasis and immunoglobulin class switch recombination. J. Exp. Med. 197: 657-667.

Hokazono, Y., Adachi, T., Wabl, M., Tada, N., Amagasa, T., and Tsubata, T. (2003): 
Inhibitory co-receptors activated by antigens but not by anti-immunoglobulin heavy 
chain antibodies install requirement of co-stimulation through CD40 for survival and 
proliferation of B cells. J. Immunol. 171: 1835-1843.


2002年以前の業績

● Wakabayashi, C., Adachi,T., Wienands,J., Tsubata,T.A distinct signaling pathway used by
the IgG-containing B cell antigen receptorScience.(2002) 298:2392-2395

抗体には、免疫応答の初期に産生されるIgM型(クラス)抗体、感染防御能の高いIgGクラスの抗体、消化管免疫に
関係するIgAクラス,寄生虫感染やアレルギーに関係するIgEクラスがあります。今回の論文では、抗体産生細胞の活
性化制御機構が抗体のクラスによって異なることを世界に先駆けて明らかにしました。この機構には膜型レクチン分
子CD22/Siglec2が関与します。この機構を人為的に制御することができるようになれば、どのようなクラスの抗体が
産生されるかを制御することが可能になります。 

論文別冊はこちら をクリック


● Higuchi, T., Aiba, Y., Nomura, T., Matsuda, J., Mochida, K., Suzuki, M., Kikutani, H., Honjo, T.,
Nishioka, K. and Tsubata T.Cutting Edge: Ectopic expression of CD40 ligand on B cells
induces lupus-like autoimmune disease. J. Immunol.(2002) 168:9-12.

●Tsubata, T.Molecular mechanisms for apoptosis induced by siganling through the B cell
antigen receptor.Int. Rev. Immunol.(2001) vol20, no.6, 675-678,791-803.

●Adachi, T., Wienands, J., Wakabayashi, C., Yakura, H., Reth, M. and Tsubata, T.SHP-1
requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated
phosphorylation of cellular substrates.J. Biol. Chem.276:26648-26655 (2001) .

●Suzuki, A., Tsukio-Yamaguchi, M., Ohteki, T., Sasaki, T., Kaisho, T., Kimura, Y., Yoshida, R.,
Wakeham, A., Higuchi, T., Fukumoto, M., Tsubata, T., Ohashi, P., Koyasu, S., Penninger, J. M.,
Nakano, T. and Mak, T. W.T cell-specific loss of Pten leads to defects in central and
peripheral tolerance. Immunity 14: 523-534 (2001)

●Tsubata, T., Wakabayashi, C. and Adachi, T.Regulation of B cell antigen receptor signaling
by CD72.In メActivating and Inhibitory Immunoglobulin-like Receptorsモ(ed. by Max D. Cooper,
Toshiyuki Takai, and Jeffrey V. Ravetch) Sprnger-Verlag Tokyo p. 123-128 (2001)

●Nagaoka, H., Takahashi, Y., Hayashi, R., Nakamura, T., Ishii, K., Matsuda, J.-I., Ogura,A.,
Shirakata, Y., Karasuyama, H., Sudo, T., Nishikawa, S.-I., Tsubata, T., Mizuochi, T., Asano, T.,
Sakano, H., Takemori, T. Ras mediates effector pathways responsible for pre-B cell survival,
which is essential for the developmental progression to the the late pre-B cell stage.J. Exp.
Med. 192: 171-181(2000)

●Yoshida, T., Higuchi, T., Hagiyama, H., Strasser, A., Nishioka, K., and Tsubata, T. Rapid B
cell apoptosis induced by antigen receptor ligation does not require Fas (CD95/APO-1), the
adapter protein FADD/MORT1 or CrmA-sensitive caspases but is defective in both MRL-+/
+ and MRL-lpr/lpr mice. Int. Immunol. 12: 517-526 (2000)

●Tsubata, T., and Honjo, T. B cell tolerance and autoimmunity. Rev. Immunogenet. 2: 18-25
(2000)

●Adachi, T., Wakabayashi, C., Nakayama, T., Yakura, H., and Tsubata T. CD72 negatively
regulates signaling through the antigen receptor of B cells. J. Immunol. 164: 1223-1229
(2000)

●Tsubata, T. Co-receptors on B lymphocytes. Curr. Opin. Immunol. 11: 249-255 (1999)

●Hagiyama, H., Adachi, T., Yoshida, T., Nomura, T, Miyasaka, N., Honjo, T., and Tsubata, T.
Signaling through the antigen receptor of B lymphocytes activates a p53-independent
pathway of c-Myc-induced apoptosis. Oncogene 18: 4091-4098 (1999)

●Tsubata, T. Apoptosis of mature B cells. Int. Rev. Immunol. 18: 347-365 (1999)

●Takeuchi, Y., Nishimura, K., Aoki, N., Adachi, T.,Sato, C., Kitajima, K., and Matsuda, T. A 42-
kDa glycoprotein from chicken egg-envelope, an avian homolog of the ZPC family
glycoproteins in mammalian Zona pellucida. Its first identification, cDNA cloning and
granulosa cell-specific expression. Eur. J. Biochm. 260: 736-742 (1999)

●Hirayama, F., Aiba, Y., Ikebuchi, K., Sekiguchi, S., and Ogawa, M. Differentiation in culture
of murine primitive lymphohematopoietic progenitors toward T-cell lineage.Blood. 93: 4187-
4195 (1999)

●Sato, T., Laver, J.H., Aiba, Y., and Ogawa, M.NK cell colony formation from human fetal
thymus. Exp. Hematol. 27: 726-733 (1999)

● Adachi, T., Flaswinkel, H., Yakura, H., Reth, M., and Tsubata, T. The B cell surface protein
CD72 recruits the tyrosine phosphatase SHP-1 upon tyrosine phosphorylation. In "
Proceedings of 10th International Congress of Immunology" (ed. by G.P.Talwar, I, Nath, N.K.
Ganguly, K.V.S.Rao) p.341-344. Monduzzi Editore S.p.A., Bologna. (1998)

●Adachi, T., Flaswinkel, H., Yakura, H., Reth, M., and Tsubata, T. The B cell surface protein
CD72 recruits the tyrosine phosphatase SHP-1 upon tyrosine phosphorylation. J. Immunol.
160: 4662-4665 (1998)

●Watanabe N., Nomura, T., Takai, T., Chiba, T., Honjo, T. and Tsubata, T. Antigen receptor
cross-linking by anti-immunoglobulin antibodies coupled to cell surface membrane induces
rapid apoptosis of normal spleen B cells. Scand. J. Immunol. 47: 541-547 (1998)

●Oubihi, M., Kitajima, K., Kobayashi, K., Adachi, T., Aoki, N., and Matsuda, T.Development of
an enzyme-linked immunosorbent assay-based method for measuring galactosyltransferase
activity using a synthetic glycopolymer acceptor substrate.Anal. Biochem. 257: 169-175
(1998)

●Hotta, H., Aoki, N., Nakamura, R., Matsuda, T. and Adachi, T. Molecular analysis of a novel
protein kinase in maturing rice seed. Gene 212: 47-54 (1998)


1997年以前の主要論文

鍔 田 武 志  Takeshii Tsubata

●Han, H., Nomura, T., Honjo, T., and Tsubata, T. 
Differential modulation of cyclin-dependent kinase inhibitor p27Kip1 by negative signaling via 
the antigen receptor of B cells and positive signaling via CD40. 
Eur. J. Immunol. 26: 2425-2432 (1996)

●Nomura, T., Han, H., Howard, M. C., Yagita, H., Yakura, H., Honjo, T., and Tsubata, T. 
Antigen receptor-mediated B cell death is blocked by signaling via CD72 or treatment with 
dextran sulfate and is defective in autoimmunity-prone mice.
Int. Immunol. 8: 867-875 (1996)

●Nisitani, S., Tsubata, T., Murakami, M., and Honjo, T.
Administration of interleukins 5 or 10 activates peritoneal B-1 cells and induces 
autoimmune hemolytic anemia in anti-erythrocyte autoantibody transgenic mice. 
Eur. J. Immunol. 25: 3047-3052 (1995) 

●Murakami, M., Tsubata, T., Shinkura, R., Nisitani, S., Okamoto, M., Yoshioka, H., Usui, T., 
Miyawaki, S. and Honjo, T.
Oral administration of lipopolysaccharides activates B-1 cells in the peritoneal cavity and 
lamina propria of the gut and induces autoimmune symptoms in an autoantibody transgenic 
mouse.
J. Exp. Med. 180: 111-121 (1994) 

●Tsubata, T., Murakami, M. and Honjo, T.
Antigen-receptor cross-linking induces peritoneal B-cell apoptosis in normal but not 
autoimmunity-prone mice. 
Curr. Biol. 4: 8-17 (1994) 

●Nisitani, S., Tsubata, T., Murakami, M., Okamoto, M. and Honjo, T.
The bcl-2 gene product inhibits clonal deletion of self-reactive B lymphocytes in the 
periphery but not in the bone marrow. 
J. Exp. Med. 178: 1247-1254 (1993) 

●Tsubata, T., Wu, J. and Honjo, T. 
B-cell apoptosis induced by antigen receptor crosslinking is blocked by T-cell signal through 
CD40. 
Nature 364: 645-648 (1993)

●Murakami, M., Tsubata, T., Okamoto, M., Shimizu, A., Kumagai, S., Imura, H. and Honjo, T.
Antigen-induced apoptotic death of Ly-1 B cells responsible for autoimmune disease in 
transgenic mice. 
Nature 357: 77-80 (1992) 

●Tsubata, T. and Nishikawa, S.-I.
Molecular and cellular aspects of early B-cell development. 
Curr. Opin. Immunol. 3: 186-192 (1991)

●Tsubata, T. and Reth, M. 
The products of pre-B specific genes (l5 and VpreB) and the immunoglobulin m chain form a 
complex that is transported onto the cell surface. 
J. Exp. Med. 172: 973-976 (1990)

●Hombach, J., Tsubata, T., Leclercq, L., Stappert, H. and Reth, M. 
Molecular components of the B-cell antigen receptor complex of the IgM class. 
Nature 343: 760-762 (1990)



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