Tasuku Honjo

Summary

Affiliation: Kyoto University
Country: Japan

Publications

  1. doi request reprint B cell-specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers
    Thinh Huy Tran
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Nat Immunol 11:148-54. 2010
  2. ncbi request reprint Separate domains of AID are required for somatic hypermutation and class-switch recombination
    Reiko Shinkura
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    Nat Immunol 5:707-12. 2004
  3. ncbi request reprint Obituary: Yasutomi Nishizuka (1932-2004)
    Tasuku Honjo
    Tasuku Honjo is in the Department of Medical Chemistry and Molecular Biology, Kyoto University Faculty of Medicine, Kyoto 6068501, Japan E mail
    Nature 432:966. 2004
  4. pmc Facilitation of beta selection and modification of positive selection in the thymus of PD-1-deficient mice
    H Nishimura
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    J Exp Med 191:891-8. 2000
  5. pmc Quantitative regulation of class switch recombination by switch region transcription
    C G Lee
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
    J Exp Med 194:365-74. 2001
  6. pmc Alymphoplasia (aly)-type nuclear factor kappaB-inducing kinase (NIK) causes defects in secondary lymphoid tissue chemokine receptor signaling and homing of peritoneal cells to the gut-associated lymphatic tissue system
    S Fagarasan
    Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Kyoto, Japan
    J Exp Med 191:1477-86. 2000
  7. ncbi request reprint Science and government. In search of the best grant system
    Tasuku Honjo
    Research Center for Science Systems, Japan Society for the Promotion of Science, Tokyo and Kyoto University, Kyoto, Japan
    Science 309:1329. 2005
  8. ncbi request reprint AID: how does it aid antibody diversity?
    Tasuku Honjo
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Immunity 20:659-68. 2004
  9. doi request reprint A memoir of AID, which engraves antibody memory on DNA
    Tasuku Honjo
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Nat Immunol 9:335-7. 2008
  10. ncbi request reprint AID to overcome the limitations of genomic information
    Tasuku Honjo
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501 Japan
    Nat Immunol 6:655-61. 2005

Collaborators

Detail Information

Publications98

  1. doi request reprint B cell-specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers
    Thinh Huy Tran
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Nat Immunol 11:148-54. 2010
    ..Our results show that Aicda is regulated by the balance between B cell-specific and stimulation-responsive elements and ubiquitous silencers...
  2. ncbi request reprint Separate domains of AID are required for somatic hypermutation and class-switch recombination
    Reiko Shinkura
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    Nat Immunol 5:707-12. 2004
    ..Thus, we propose that separate domains of AID interact with specific cofactors to regulate these two distinct genetic events in a target-specific way...
  3. ncbi request reprint Obituary: Yasutomi Nishizuka (1932-2004)
    Tasuku Honjo
    Tasuku Honjo is in the Department of Medical Chemistry and Molecular Biology, Kyoto University Faculty of Medicine, Kyoto 6068501, Japan E mail
    Nature 432:966. 2004
  4. pmc Facilitation of beta selection and modification of positive selection in the thymus of PD-1-deficient mice
    H Nishimura
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    J Exp Med 191:891-8. 2000
    ..These results collectively indicate that PD-1 negatively regulates the beta selection and modulates the positive selection, and suggest that PD-1 deficiency may lead to the significant alteration of mature T cell repertoire...
  5. pmc Quantitative regulation of class switch recombination by switch region transcription
    C G Lee
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
    J Exp Med 194:365-74. 2001
    ..Such structures may be recognition targets of a putative class switch recombinase...
  6. pmc Alymphoplasia (aly)-type nuclear factor kappaB-inducing kinase (NIK) causes defects in secondary lymphoid tissue chemokine receptor signaling and homing of peritoneal cells to the gut-associated lymphatic tissue system
    S Fagarasan
    Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Kyoto, Japan
    J Exp Med 191:1477-86. 2000
    ....
  7. ncbi request reprint Science and government. In search of the best grant system
    Tasuku Honjo
    Research Center for Science Systems, Japan Society for the Promotion of Science, Tokyo and Kyoto University, Kyoto, Japan
    Science 309:1329. 2005
  8. ncbi request reprint AID: how does it aid antibody diversity?
    Tasuku Honjo
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Immunity 20:659-68. 2004
    ..Recent findings, namely requirement of protein synthesis for DNA breakage and dispensability of U removal activity of uracil DNA glycosylase, force us to reconsider DNA deamination hypothesis...
  9. doi request reprint A memoir of AID, which engraves antibody memory on DNA
    Tasuku Honjo
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Nat Immunol 9:335-7. 2008
  10. ncbi request reprint AID to overcome the limitations of genomic information
    Tasuku Honjo
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501 Japan
    Nat Immunol 6:655-61. 2005
    ..Although a series of experiments has provided support for the 'RNA-editing' hypothesis and requires reevaluation of the 'DNA-deamination' hypothesis, definitive proof is yet to come...
  11. ncbi request reprint Molecular mechanism of class switch recombination: linkage with somatic hypermutation
    Tasuku Honjo
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    Annu Rev Immunol 20:165-96. 2002
    ..Mismatched bases will be corrected or fixed by mismatch repair enzymes. CSR ends are then ligated by the NHEJ system while SHM nicks are repaired by another ligation system...
  12. doi request reprint PD-1 deficiency results in the development of fatal myocarditis in MRL mice
    Jian Wang
    Department of Immunology and Genomic Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Japan
    Int Immunol 22:443-52. 2010
    ..These findings unravel the hidden heart-specific autoimmune predisposition of MRL mice and provide MRL-Pdcd1(-)(/-) mice as a useful animal model of lymphocytic myocarditis...
  13. doi request reprint Identification of QTLs that modify peripheral neuropathy in NOD.H2b-Pdcd1-/- mice
    Fang Jiang
    Department of Immunology and Genomic Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Int Immunol 21:499-509. 2009
    ..These results indicate that NOD genetic background harbors various QTLs that modify autoimmune phenotypes either by organ-specific or by organ-non-specific manner...
  14. pmc Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade
    Yoshiko Iwai
    Department of Medical Chemistry, Graduate School of Medicine, Japan Science and Technology Corporation, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 99:12293-7. 2002
    ....
  15. pmc The C-terminal region of activation-induced cytidine deaminase is responsible for a recombination function other than DNA cleavage in class switch recombination
    Tomomitsu Doi
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 106:2758-63. 2009
    ..Therefore, AID does not distinguish between the V and S regions for cleavage, but carries another function specific to CSR...
  16. ncbi request reprint Estrogen promotes differentiation and survival of dopaminergic neurons derived from human neural stem cells
    Yo Kishi
    Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
    J Neurosci Res 79:279-86. 2005
    ..These results support a possible role for estrogen in the transplantation of NSCs for Parkinson's disease...
  17. ncbi request reprint AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts
    Kiyotsugu Yoshikawa
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida konoe cho, Sakyo ku, Kyoto, 606 8501, Japan
    Science 296:2033-6. 2002
    ..These results indicate that AID is sufficient for the generation of SHM in an actively transcribed gene in fibroblasts, as well as B cells, and that any of the required cofactors must be present in these fibroblasts...
  18. pmc De novo protein synthesis is required for the activation-induced cytidine deaminase function in class-switch recombination
    Tomomitsu Doi
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 100:2634-8. 2003
    ..The results lend the weight to RNA-editing hypothesis for the function of AID...
  19. pmc RNA-editing cytidine deaminase Apobec-1 is unable to induce somatic hypermutation in mammalian cells
    Tomonori Eto
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida konoe cho, Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 100:12895-8. 2003
    ..Unlike AID, Apobec-1 was unable to induce somatic hypermutation or class switching. The results force a reevaluation of the physiological significance of the DNA deaminase activities of AID and Apobec-1 in E. coli and in vitro...
  20. pmc Msx2-interacting nuclear target protein (Mint) deficiency reveals negative regulation of early thymocyte differentiation by Notch/RBP-J signaling
    Masayuki Tsuji
    Department of Immunology, Kyoto University Graduate School of Medicine, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 104:1610-5. 2007
    ..Unexpectedly, however, Mint deficiency impairs differentiation of ETP into DN2 cells, suggesting that Notch/RBP-J signaling negatively regulates DN1-DN2 transition...
  21. pmc DNA cleavage in immunoglobulin somatic hypermutation depends on de novo protein synthesis but not on uracil DNA glycosylase
    Hitoshi Nagaoka
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 102:2022-7. 2005
    ..The requirement of protein synthesis but not of UNG for the DNA cleavage step of SHM forces us to reconsider the DNA deamination hypothesis and strengthens the RNA editing hypothesis...
  22. ncbi request reprint Generation of a conditional knockout allele for mammalian Spen protein Mint/SHARP
    Daisuke Yabe
    Department of Medical Chemistry and Molecular Biology, Kyoto University Graduate School of Medicine, Kyoto, Japan
    Genesis 45:300-6. 2007
    ..In addition, Mint deficiency caused severe hypoplasia in postnatal brain, suggesting it may regulate neuronal cell survival...
  23. ncbi request reprint Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora
    Sidonia Fagarasan
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    Science 298:1424-7. 2002
    ..Because an inability to switch to immunoglobulin A on its own does not lead to a similar phenotype, these results suggest that SHM of ILF B cells plays a critical role in regulating intestinal microflora...
  24. pmc AID-induced decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch recombination
    Maki Kobayashi
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 106:22375-80. 2009
    ..Taken together, AID-induced Top1 reduction alters S region DNA structure probably to non-B form, on which Top1 can introduce nicks but cannot religate, resulting in S region cleavage...
  25. doi request reprint Organ-specific profiles of genetic changes in cancers caused by activation-induced cytidine deaminase expression
    Toshiyuki Morisawa
    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Int J Cancer 123:2735-40. 2008
    ..Our findings suggest that AID, a DNA mutator that plays a critical role linking inflammation to human cancers, might be involved in the generation of organ-specific genetic diversity in oncogenic pathways during cancer development...
  26. pmc Molecular mechanism for generation of antibody memory
    Velizar Shivarov
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Philos Trans R Soc Lond B Biol Sci 364:569-75. 2009
    ..We also provide further evidence that UNG plays a non-canonical role in CSR, namely in the repair step of the DNA breaks. Taking these results together, we favour the RNA-editing model for the function of AID in CSR...
  27. ncbi request reprint Uracil DNA glycosylase activity is dispensable for immunoglobulin class switch
    Nasim A Begum
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Science 305:1160-3. 2004
    ..These results indicate that UNG is involved in the repair step of CSR yet by an unknown mechanism. The dispensability of U removal in the DNA cleavage step of CSR requires a reconsideration of the model of DNA deamination by AID...
  28. pmc Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice
    Ai Kotani
    Department of Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 104:1616-20. 2007
    ..Thus, AID may play multiple roles in B cell lymphomagenesis...
  29. pmc The histone chaperone Spt6 is required for activation-induced cytidine deaminase target determination through H3K4me3 regulation
    Nasim A Begum
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    J Biol Chem 287:32415-29. 2012
    ..We conclude that Spt6 is a unique histone chaperone capable of regulating the histone epigenetic state of both AID targets and the AID locus...
  30. ncbi request reprint Specific and high-affinity binding of tetramerized PD-L1 extracellular domain to PD-1-expressing cells: possible application to enhance T cell function
    Seigo Terawaki
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Int Immunol 19:881-90. 2007
    ..The results suggest that oligomeric PD-L1 extracellular domains may provide a potential means to restore T cell functions in cancer and viral infection in humans...
  31. ncbi request reprint Regulation of alphabeta/gammadelta T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling
    Kenji Tanigaki
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto, 606 8501, Japan
    Immunity 20:611-22. 2004
    ..Our data demonstrated that Notch/RBP-J signaling regulates gammadelta T cell generation and migration, alphabeta T cell maturation, terminal differentiation of CD4(+) T cells into Th1/Th2 cells, and activation of T cells...
  32. pmc A target selection of somatic hypermutations is regulated similarly between T and B cells upon activation-induced cytidine deaminase expression
    Ai Kotani
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida konoe cho, Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 102:4506-11. 2005
    ..SHM base specificities in the CD4 and CD5 genes were biased to AT, indicating that the preference of target bases of the mutations generated by overexpression of AID is not always GC bases but variable between target genes...
  33. pmc Constitutive expression of AID leads to tumorigenesis
    Il Mi Okazaki
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida konoe cho, Sakyo ku, Kyoto 606 8501, Japan
    J Exp Med 197:1173-81. 2003
    ..The results indicate that AID can mutate non-Ig genes including oncogenes, implying that aberrant AID expression could be a cause of human malignancy...
  34. ncbi request reprint AID mutant analyses indicate requirement for class-switch-specific cofactors
    Van Thanh Ta
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto, 606 8501, Japan
    Nat Immunol 4:843-8. 2003
    ..These results indicate that AID requires interaction with a cofactor(s) specific to CSR...
  35. ncbi request reprint Discovery of activation-induced cytidine deaminase, the engraver of antibody memory
    Masamichi Muramatsu
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Adv Immunol 94:1-36. 2007
    ..In addition, UNG appears to have a noncanonical function through interaction with an HIV Vpr-like protein at the WXXF motif. Taken together, RNA editing hypothesis is gaining the ground...
  36. ncbi request reprint Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice
    Taku Okazaki
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto, 606 8501, Japan
    Nat Med 9:1477-83. 2003
    ..These findings suggest that antibodies to cTnI induce heart dysfunction and dilatation by chronic stimulation of Ca2+ influx in cardiomyocytes...
  37. pmc Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut
    Keiichiro Suzuki
    Departments of Medical Chemistry and Gastroenterology, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 101:1981-6. 2004
    ....
  38. pmc PD-1 inhibits antiviral immunity at the effector phase in the liver
    Yoshiko Iwai
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    J Exp Med 198:39-50. 2003
    ..These results indicate that PD-1 plays an important role in T cell tolerance at the effector phase and the blockade of the PD-1 pathway can augment antiviral immunity...
  39. ncbi request reprint Neural precursor cells derived from human embryonic brain retain regional specificity
    Satoshi Horiguchi
    Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
    J Neurosci Res 75:817-24. 2004
    ..These results suggest that human neural precursor cells might have the potential to differentiate into a variety of cells but retain regional specificity...
  40. pmc Negative regulation of activation-induced cytidine deaminase in B cells
    Taro Muto
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 103:2752-7. 2006
    ....
  41. pmc Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/- mice
    Taku Okazaki
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    J Exp Med 202:1643-8. 2005
    ..These observations suggest cross talk between two immunoinhibitory receptors, FcgammaRIIB and PD-1, on the regulation of autoimmune diseases...
  42. pmc Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation
    Il Mi Okazaki
    Department of Immunology and Genomic Medicine, Frontier Technology Center, Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 108:7920-5. 2011
    ..These results suggest that Spt6 is involved in differential regulation of CSR and SHM by AID...
  43. pmc Accumulation of the FACT complex, as well as histone H3.3, serves as a target marker for somatic hypermutation
    Masatoshi Aida
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 110:7784-9. 2013
    ..The regions with the most abundant deposition of FACT and H3.3 were also the most efficient targets of SHM. These results demonstrate the importance of histone-exchanging dynamics at the chromatin of SHM targets, especially in Ig genes...
  44. doi request reprint TRIM28 prevents autoinflammatory T cell development in vivo
    Shunsuke Chikuma
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Nat Immunol 13:596-603. 2012
    ..Notably, CKO Foxp3(+) T cells were unable to prevent the autoimmune phenotype in vivo. Our results show critical roles for TRIM28 in both T cell activation and T cell tolerance...
  45. doi request reprint An evolutionary view of the mechanism for immune and genome diversity
    Lucia Kato
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    J Immunol 188:3559-66. 2012
    ..Thus, the risk of introducing genome instability into nonimmunoglobulin loci is unavoidable but tolerable compared with the advantage conferred on the host of being protected against pathogens by the enormous Ig diversification...
  46. doi request reprint Activation-induced cytidine deaminase links between inflammation and the development of colitis-associated colorectal cancers
    Yoko Endo
    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Gastroenterology 135:889-98, 898.e1-3. 2008
    ..In the current study, we investigated whether AID might contribute to the development of colitis-associated colorectal cancers...
  47. ncbi request reprint Requirement of non-canonical activity of uracil DNA glycosylase for class switch recombination
    Nasim A Begum
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    J Biol Chem 282:731-42. 2007
    ..These results suggest that UNG is recruited to the CSR machinery through its WXXF motif by a Vpr-like host factor and plays a novel non-canonical role in a CSR step that follows DNA cleavage...
  48. ncbi request reprint Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision
    Hua Han
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    Int Immunol 14:637-45. 2002
    ..Myeloid and B lineage differentiation appears normal in the bone marrow of RBP-J-inactivated mice. These results suggest that RBP-J, probably by mediating Notch signaling, controls T versus B cell fate decision in lymphoid progenitors...
  49. doi request reprint PD-1-mediated suppression of IL-2 production induces CD8+ T cell anergy in vivo
    Shunsuke Chikuma
    Department of Immunology and Genetic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    J Immunol 182:6682-9. 2009
    ....
  50. doi request reprint Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes
    Zahra Sabouri
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida, Kyoto, Japan
    Int Immunol 21:947-55. 2009
    ..In addition, Apex1 knockdown in CH12F3-2 B lymphoma cells did not affect the CSR frequency, suggesting that neither Apex1 nor Apex2 plays a major role in CSR...
  51. ncbi request reprint Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway
    Kazuki Kuroda
    Department of Medical Chemistry, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Immunity 18:301-12. 2003
    ..MINT may serve as a functional homolog of Drosophila Hairless...
  52. ncbi request reprint Functional assessment of self-renewal activity of male germline stem cells following cytotoxic damage and serial transplantation
    Mito Kanatsu-Shinohara
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Japan
    Biol Reprod 68:1801-7. 2003
    ..8- and 12-fold within 2 and 4 mo, respectively. These results provide direct functional evidence for the expansion of stem cells and establish the basis for further characterization of the stem cell self-renewal process...
  53. pmc De novo protein synthesis is required for activation-induced cytidine deaminase-dependent DNA cleavage in immunoglobulin class switch recombination
    Nasim A Begum
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 101:13003-7. 2004
    ..Requirement of protein synthesis in the DNA cleavage step of CSR strengthens the RNA-editing hypothesis...
  54. ncbi request reprint Identification of a specific domain required for dimerization of activation-induced cytidine deaminase
    Jishu Wang
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    J Biol Chem 281:19115-23. 2006
    ..Dimer formation and its requirement for the function of AID are features that AID shares with APOBEC-1, an RNA editing enzyme of apolipoprotein B100 mRNA...
  55. ncbi request reprint Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues
    Masayoshi Ishida
    Laboratory of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606 8501, Japan
    Immunol Lett 84:57-62. 2002
    ..Thus, present results demonstrate the distinct expression patterns of PD-L1 and PD-L2 with the cells of lymphohematopoietic tissues exclusively expressing the former...
  56. doi request reprint Preventing AID, a physiological mutator, from deleterious activation: regulation of the genomic instability that is associated with antibody diversity
    Hitoshi Nagaoka
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Int Immunol 22:227-35. 2010
    ..This is probably because immediate protection against pathogens is more critical for species survival than complete protection from the slower acting consequences of genomic instability, such as tumor formation...
  57. pmc Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes
    Jian Wang
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 102:11823-8. 2005
    ....
  58. pmc Decrease in topoisomerase I is responsible for activation-induced cytidine deaminase (AID)-dependent somatic hypermutation
    Maki Kobayashi
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 108:19305-10. 2011
    ..We speculate that the mechanism for transcription-coupled genome instability was adopted to generate immune diversity when AID evolved...
  59. doi request reprint The AID dilemma: infection, or cancer?
    Tasuku Honjo
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto, Japan
    Adv Cancer Res 113:1-44. 2012
    ..In the interest of survival, vertebrates must have evolved AID to prevent infection despite its long-term risk of causing tumorigenesis...
  60. ncbi request reprint Role of AID in tumorigenesis
    Il Mi Okazaki
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Adv Immunol 94:245-73. 2007
    ....
  61. pmc PD-1 deficiency reveals various tissue-specific autoimmunity by H-2b and dose-dependent requirement of H-2g7 for diabetes in NOD mice
    Taku Yoshida
    Department of Immunology and Genomic Medicine, 21st Century Center of Excellence Formation, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto, 606 8501, Japan
    Proc Natl Acad Sci U S A 105:3533-8. 2008
    ..In addition, 60% of the NOD-H2(b/g7)Pdcd1(-/-) mice developed diabetes, suggesting that H-2(b) does not dominantly suppress diabetes and that H-2(g7) induces diabetes in a dose-dependent fashion...
  62. pmc Activation-induced deaminase (AID)-directed hypermutation in the immunoglobulin Smu region: implication of AID involvement in a common step of class switch recombination and somatic hypermutation
    Hitoshi Nagaoka
    Department of Medical Chemistry Graduate School of Medicine, Kyoto University, Yoshida konoe cho, Sakyo ku, Kyoto 606 8501, Japan
    J Exp Med 195:529-34. 2002
    ..These findings strongly suggest that AID itself or a single molecule generated by RNA editing function of AID may mediate a common step of SHM and CSR, which is likely to be involved in DNA cleavage...
  63. ncbi request reprint New regulatory co-receptors: inducible co-stimulator and PD-1
    Taku Okazaki
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto, Japan
    Curr Opin Immunol 14:779-82. 2002
    ..PD-1 deficient mice develop lupus-like glomerulonephritis and arthritis on a C57Bl/6 background and autoimmune-dilated cardiomyopathy on a BALB/c background...
  64. doi request reprint Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signaling
    Masahiro Kido
    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Gastroenterology 135:1333-43. 2008
    ..This study aims to examine the regulatory roles of naturally arising CD4(+)CD25(+) regulatory T (Treg) cells and programmed cell death 1 (PD-1)-mediated signaling in the development of AIH...
  65. ncbi request reprint Multiple roles of Notch signaling in cochlear development
    Shinji Takebayashi
    Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoinkawahara cho, Sakyo ku, Kyoto 606 8507, Japan
    Dev Biol 307:165-78. 2007
    ..Second, Notch signaling is required for the induction of Prox1-positive supporting cells. Third, Notch signaling is required for the maintenance of supporting cells...
  66. pmc Activation-induced cytidine deaminase shuttles between nucleus and cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1
    Satomi Ito
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 101:1975-80. 2004
    ....
  67. ncbi request reprint Regulation of AID function in vivo
    Reiko Shinkura
    Department of Immunology and Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan 606 8501
    Adv Exp Med Biol 596:71-81. 2007
  68. ncbi request reprint PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells
    Yoshiko Iwai
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    Int Immunol 17:133-44. 2005
    ..These results suggest that PD-1 blockade may be a powerful tool for treatment of hematogenous spread of various tumor cells...
  69. ncbi request reprint Rejuvenating exhausted T cells during chronic viral infection
    Taku Okazaki
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto, 606 8501, Japan
    Cell 124:459-61. 2006
    ..Remarkably, blocking the interaction between PD-1 and its ligand, PD-L1, reactivates these T cells and reduces viral load...
  70. ncbi request reprint Regulation of B cell development by Notch/RBP-J signaling
    Kenji Tanigaki
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Semin Immunol 15:113-9. 2003
    ..Studies on RBP-J conditional knockout mice that have lost MZ B cells without affecting Fo B cell functions have shown that MZ B cells play pivotal roles in immune responses to blood-borne bacteria...
  71. ncbi request reprint Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium
    Yuko Matsumoto
    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara cho, Shogoin, Sakyo ku, Kyoto 606 8507, Japan
    Nat Med 13:470-6. 2007
    ..Our findings provide evidence that aberrant AID expression caused by H. pylori infection might be a mechanism of mutation accumulation in the gastric mucosa during H. pylori-associated gastric carcinogenesis...
  72. ncbi request reprint The AID enzyme induces class switch recombination in fibroblasts
    Il Mi Okazaki
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida konoe cho, Sakyo ku, Kyoto 606 8501, Japan
    Nature 416:340-5. 2002
    ..The results show that AID is the only B-cell-specific factor required for initiation of the CSR reaction in the activated locus...
  73. ncbi request reprint Regulation of IgA synthesis at mucosal surfaces
    Sidonia Fagarasan
    RIKEN Research Center for Allergy and Immunology, Tsurumi ku, Yokohama, Kanagawa 230 0045, Japan
    Curr Opin Immunol 16:277-83. 2004
    ..Recent advances in this field include new insights into the role of IgA in the maintenance of gut homeostasis and the proposal of an updated model for the induction of IgA responses in the gut...
  74. pmc Carboxy-terminal domain of AID required for its mRNA complex formation in vivo
    Taichiro Nonaka
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 106:2747-51. 2009
    ..These results suggest that the CSR activity of AID requires an ACF-like cofactor that specifically interacts with the carboxy-terminal domain of AID...
  75. ncbi request reprint Evolution of class switch recombination function in fish activation-induced cytidine deaminase, AID
    Koshou Wakae
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Int Immunol 18:41-7. 2006
    ..We discuss how pleiotropic functions of specific domains within the AID protein may have facilitated the early evolution of CSR in lower vertebrates...
  76. pmc Dissociation of in vitro DNA deamination activity and physiological functions of AID mutants
    Velizar Shivarov
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 105:15866-71. 2008
    ..These results indicate that DNA deamination activity does not represent the physiological function of AID...
  77. ncbi request reprint Intestinal IgA synthesis: regulation of front-line body defences
    Sidonia Fagarasan
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    Nat Rev Immunol 3:63-72. 2003
    ..In addition, we discuss new insights into the role of IgA in the maintenance of gut homeostasis and into the reciprocal interactions between gut B cells and the bacterial flora...
  78. pmc Further evidence for involvement of a noncanonical function of uracil DNA glycosylase in class switch recombination
    Nasim A Begum
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 106:2752-7. 2009
    ..The present findings support our earlier proposal that CSR depends on a noncanonical function of the UNG protein (e.g., as a scaffold for repair enzymes) that might be required for the recombination reaction after DNA cleavage...
  79. ncbi request reprint The 20th IUBMB International Congress in Kyoto
    Koichi Ikuta
    Department of Immunology and Genomic Medicine, Kyoto University, Graduate School of Medicine, Yoshida, Kyoto, Japan
    IUBMB Life 58:258. 2006
  80. pmc Activation and differentiation of autoreactive B-1 cells by interleukin 10 induce autoimmune hemolytic anemia in Fas-deficient antierythrocyte immunoglobulin transgenic mice
    Norihiko Watanabe
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    J Exp Med 196:141-6. 2002
    ..These results suggest that activation of B-1 cells is responsible for induction of AIHA in Fas-deficient condition and that IL-10 plays a critical role in terminal differentiation of B-1 cells in these mice...
  81. doi request reprint Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense
    Min Wei
    Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Nat Immunol 12:264-70. 2011
    ..Together our results indicate that SHM is critical in maintaining intestinal homeostasis and efficient mucosal defense...
  82. ncbi request reprint Stem cell-derived neural stem/progenitor cell supporting factor is an autocrine/paracrine survival factor for adult neural stem/progenitor cells
    Hiroki Toda
    Department of Medical Chemistry, Kyoto University Graduate School of Medicine, Yoshida konoe cho, Sakyoku, Kyoto 606 8501, Japan
    J Biol Chem 278:35491-500. 2003
    ..These data suggested an important role of SDNSF as an autocrine/paracrine factor in maintaining stem cell potential and lifelong neurogenesis in adult central nervous system...
  83. ncbi request reprint Microanatomical localization of PD-1 in human tonsils
    Yoshiko Iwai
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    Immunol Lett 83:215-20. 2002
    ..These results suggest that PD-1 may play an important role in GC reaction...
  84. ncbi request reprint Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells
    Kenji Tanigaki
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto, 606 8501, Japan
    Nat Immunol 3:443-50. 2002
    ..In contrast, these mice exhibited increased mortality rates after blood-borne bacterial infection, which indicates that MZB cells play pivotal roles in the clearance of these bacteria...
  85. ncbi request reprint Type two hyper-IgM syndrome caused by mutation in activation-induced cytidine deaminase
    Yi Zhu
    Department of Human Ontogeny and Childhood Development, Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan
    J Med Dent Sci 50:41-6. 2003
    ....
  86. ncbi request reprint AID is required for c-myc/IgH chromosome translocations in vivo
    Almudena R Ramiro
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA
    Cell 118:431-8. 2004
    ..Here we report that AID is essential for the c-myc/IgH chromosome translocations induced by IL6...
  87. pmc Unmutated immunoglobulin M can protect mice from death by influenza virus infection
    Yuichi Harada
    Department of Virology and Immunology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan
    J Exp Med 197:1779-85. 2003
    ....
  88. pmc DNA double-strand breaks: prior to but not sufficient in targeting hypermutation
    Linda Bross
    Basel Institute for Immunology, CH 4005 Basel, Switzerland
    J Exp Med 195:1187-92. 2002
    ..The possible roles of DSBs in relation to AID function and SHM are discussed...
  89. ncbi request reprint Does AID need another aid?
    Tasuku Honjo
    Nat Immunol 3:800-1. 2002
  90. pmc AID-deficient Bcl-xL transgenic mice develop delayed atypical plasma cell tumors with unusual Ig/Myc chromosomal rearrangements
    Alexander L Kovalchuk
    Laboratory of Cancer Biology and Genetics, Cancer Genomics Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 204:2989-3001. 2007
    ..In contrast, the second was T(12;15) negative, but had an elevated N-Myc expression caused by a paracentric inversion of chromosome 12. Thus, novel mechanisms juxtapose Ig and Myc-family genes in AID-deficient plasma cell tumors...
  91. ncbi request reprint Cutting Edge: Ectopic expression of CD40 ligand on B cells induces lupus-like autoimmune disease
    Tetsuya Higuchi
    Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8510, Japan
    J Immunol 168:9-12. 2002
    ..Thus, ectopic CD40L expression on B cells may play a crucial role in development of SLE...
  92. ncbi request reprint AID-/-mus-/- mice are agammaglobulinemic and fail to maintain B220-CD138+ plasma cells
    Kaori Kumazaki
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    J Immunol 178:2192-203. 2007
    ..We found no evidence that this reduced survival was attributable to accumulation of membrane IgM. Our results indicate that the synthesis of secretory Igs is a requirement for maintenance of B220(-)CD138(+) PCs...
  93. ncbi request reprint Absence of programmed death receptor 1 alters thymic development and enhances generation of CD4/CD8 double-negative TCR-transgenic T cells
    Christian Blank
    Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 171:4574-81. 2003
    ..Our results are consistent with a model in which absence of PD-1 leads to greater negative selection of strongly interacting DP cells as well as increased emergence of DN alphabeta peripheral T cells...
  94. ncbi request reprint B1b lymphocytes confer T cell-independent long-lasting immunity
    Kishore R Alugupalli
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655, USA
    Immunity 21:379-90. 2004
    ..These data demonstrate that B1b lymphocytes can provide long-lasting T cell-independent IgM memory...
  95. ncbi request reprint Regulation of lymphocyte development by Notch signaling
    Kenji Tanigaki
    Research Institute, Shiga Medical Center, 5 4 30 Moriyama, Moriyama shi, Shiga 524 8524 Japan
    Nat Immunol 8:451-6. 2007
    ..Here we highlight parallels in the developmental regulation of mammalian lymphocytes and the D. melanogaster nervous system through Notch cooperation with the transcriptional regulators RBP-J (Su(H)), MINT (Hairless) and E2A (Ac-Sc-Da)...
  96. ncbi request reprint AID is required for germinal center-derived lymphomagenesis
    Laura Pasqualucci
    Institute for Cancer Genetics, the Departments of Pathology and Genetics and Development, and The Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA
    Nat Genet 40:108-12. 2008
    ..These results show that AID is required for GC-derived lymphomagenesis, supporting the notion that errors in AID-mediated antigen-receptor gene modification processes are principal contributors to the pathogenesis of human B-NHL...
  97. pmc Two distinctive pathways for recruitment of naive and primed IgM+ B cells to the gut lamina propria
    Keiichiro Suzuki
    RIKEN Research Center for Allergy and Immunology, Tsurumi ku, Yokohama, Kanagawa 230 0045, Japan
    Proc Natl Acad Sci U S A 102:2482-6. 2005
    ..By contrast, the entry of gut-primed IgM+ B cells to the LP is independent of stromal cells with functional NIK. Our results indicate that naive B cells directly migrate to the LP by a distinct pathway from gut-primed B cells...
  98. ncbi request reprint The canonical Notch/RBP-J signaling pathway controls the balance of cell lineages in mammary epithelium during pregnancy
    Krista D Buono
    Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Dev Biol 293:565-80. 2006
    ..We propose that the Notch-RBP-J pathway regulates alveolar development during pregnancy by maintaining luminal cell fate and preventing uncontrolled basal cell proliferation...