Research Summary

My laboratory studies receptor signaling in immune cells with a focus on the B cell antigen receptor (BCR) and Toll-like receptors (TLRs). In a longstanding collaboration with Clifford Lowell (UCSF), we have also studied the role of the Src-family kinase Lyn in inhibitory receptor signaling in B cells and the autoimmune disease that develops in Lyn-deficient mice. To study the in vivo function of TLRs in mice, we made a conditional (Cre/loxP) allele of the TLR signaling component MyD88 and have used this tool to characterize the role of MyD88 in dendritic cells and B cells for innate and adaptive immune responses. In recent years, we have discovered that BCR and TLR signaling reactions synergize to promote the germinal center response.

Research Funding

  • September 1, 1988 - July 31, 2024 - Molecular and Cellular Immunology , Principal Investigator . Sponsor: NIH, Sponsor Award ID: T32AI007334
  • March 1, 2018 - February 28, 2023 - Organ-specific autoimmunity resulting from two genetic defects in tolerance , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI138479
  • July 1, 2015 - June 30, 2017 - B cell TLRs and germinal centers , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AI117378
  • July 1, 2013 - June 30, 2016 - The role of Apobec3 enzymes in regulation of marginal zone B cells , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AI107101

Education

Harvard College, Cambridge MA, A.B., 1975, Biochemical & Molecular Biology
University of California, Berkeley, CA, Ph.D., 1979, Biochemistry
National Institutes of Health, Bethesda MD, Postdoctoral, 1979-83, Immunology

Honors & Awards

  • 1974
    Dreyfuss Foundation Fellow
  • 1975
    Phi Beta Kappa, Harvard University
  • 1975-78
    NSF Predoctoral Fellow
  • 1979-82
    Helen Hay Whitney Postdoctoral Fellow; 2nd Rose Lieberman Lecturer, NIH 10/93
  • 1994
    NIAID Merit Award
  • 1997-98
    NIH Fogarty Senior International Award

Selected Publications

  1. Mianmian Yin, Jennifer A Smith, Marissa Chou, Jackie Chan, Yongmei Hu, Clifford A Lowell, Douglas B Gould, Mark S Anderson, Anthony L DeFranco. Autoantigen specific T-cell receptor induces organ-specific autoimmunity by escaping T cell negative selection. The Journal of Immunology. 2022 May 1; 208(1_Supplement):104.02-104.02.  View on PubMed
  2. Mianmian Yin, Kamir J Hiam, Irina Proekt, Jackie Chan, Yongmei Hu, Clifford A Lowell, Douglas B Gould, Matthew Spitzer, Mark S Anderson, Anthony L DeFranco. Development of uveitis in a mouse model of spontaneous autoimmunity correlates with frequency of autoantigen-specific regulatory T cells. The Journal of Immunology. 2022 May 1; 208(1_Supplement):44.07-44.07.  View on PubMed
  3. Mianmian Yin, Kamir Hiam, Irina Proekt, Jackie Chan, Yongmei Hu, Clifford A Lowell, Douglas B Gould, Mark S Anderson, Anthony L DeFranco. Correlation of autoantigen-specific Treg frequency with development of spontaneous organ-specific autoimmunity in a mouse model of uveitis. The Journal of Immunology. 2021 May 1; 206(1_Supplement):51.05-51.05.  View on PubMed
  4. Mianmian Yin, Jennifer A Smith, Marissa Chou, Jackie Chan, Yongmei Hu, Clifford A Lowell, Douglas B Gould, Mark S Anderson, Anthony L DeFranco. T-cell receptor repertoire of mice with organ-specific autoimmunity resulting from a partial defect in T cell negative selection and dendritic cell enhancement. The Journal of Immunology. 2021 May 1; 206(1_Supplement):51.06-51.06.  View on PubMed
  5. Anthony L DeFranco, Alexander J Finn, Julie Hambleton, Mary T Crowley, Mary Lee MacKichan, Steven L Weinstein. The Role of MAP Kinases, Phosphatidylinositol 3-Kinase, and Ceramide in LPS-induced Signaling in Macrophages. . 2020 Oct 23; 473-482.  View on PubMed
  6. Wigton EJ, DeFranco AL, Ansel KM. Antigen Complexed with a TLR9 Agonist Bolsters c-Myc and mTORC1 Activity in Germinal Center B Lymphocytes. Immunohorizons. 2019 08 19; 3(8):389-401.  View on PubMed
  7. Faggioni M, Baber U, Chandrasekhar J, Sartori S, Claessen BE, Rao SV, Vogel B, Effron MB, Poddar K, Farhan S, Kini A, Weintraub W, Toma C, Sorrentino S, Weiss S, Snyder C, Muhlestein JB, Kapadia S, Keller S, Strauss C, Aquino M, Baker B, Defranco A, Pocock S, Henry T, Mehran R. Use of prasugrel vs clopidogrel and outcomes in patients with and without diabetes mellitus presenting with acute coronary syndrome undergoing percutaneous coronary intervention. Int J Cardiol. 2019 Jan 15; 275:31-35.  View on PubMed
  8. DeFranco AL. Multilayer Control of B Cell Activation by the B Cell Antigen Receptor: Following Themes Initiated With Bill Paul. Front Immunol. 2018; 9:739.  View on PubMed
  9. Tian M, Hua Z, Hong S, Zhang Z, Liu C, Lin L, Chen J, Zhang W, Zhou X, Zhang F, DeFranco AL, Hou B. B Cell-Intrinsic MyD88 Signaling Promotes Initial Cell Proliferation and Differentiation To Enhance the Germinal Center Response to a Virus-like Particle. J Immunol. 2018 02 01; 200(3):937-948.  View on PubMed
  10. Costa S, Marini O, Bevilacqua D, DeFranco AL, Hou B, Lonardi S, Vermi W, Rodegher P, Panato A, Tagliaro F, Lowell CA, Cassatella MA, Girolomoni G, Scapini P. Role of MyD88 signaling in the imiquimod-induced mouse model of psoriasis: focus on innate myeloid cells. J Leukoc Biol. 2017 09; 102(3):791-803.  View on PubMed
  11. DeFranco AL. Innate B cells cleave to the marginal zone. Nat Immunol. 2017 02 15; 18(3):248-250.  View on PubMed
  12. Lee LM, Ji M, Sinha M, Dong MB, Ren X, Wang Y, Lowell CA, Ghosh S, Locksley RM, DeFranco AL. Determinants of Divergent Adaptive Immune Responses after Airway Sensitization with Ligands of Toll-Like Receptor 5 or Toll-Like Receptor 9. PLoS One. 2016; 11(12):e0167693.  View on PubMed
  13. Proekt I, Miller CN, Jeanne M, Fasano KJ, Moon JJ, Lowell CA, Gould DB, Anderson MS, DeFranco AL. LYN- and AIRE-mediated tolerance checkpoint defects synergize to trigger organ-specific autoimmunity. J Clin Invest. 2016 10 03; 126(10):3758-3771.  View on PubMed
  14. DeFranco AL. Germinal centers and autoimmune disease in humans and mice. Immunol Cell Biol. 2016 11; 94(10):918-924.  View on PubMed
  15. Wang H, Li M, Hung CY, Sinha M, Lee LM, Wiesner DL, LeBert V, Lerksuthirat T, Galles K, Suresh M, DeFranco AL, Lowell CA, Klein BS, Wüthrich M. MyD88 Shapes Vaccine Immunity by Extrinsically Regulating Survival of CD4+ T Cells during the Contraction Phase. PLoS Pathog. 2016 08; 12(8):e1005787.  View on PubMed
  16. DeFranco AL. The germinal center antibody response in health and disease. F1000Res. 2016; 5.  View on PubMed
  17. Irina Proekt, Corey Miller, Marion Jeanne, Kayla Fasano, Clifford A Lowell, Douglas Gould, Mark S Anderson, Anthony L DeFranco. Triggering of organ-specific autoimmunity through synergy of defects in key tolerance checkpoints. The Journal of Immunology. 2016 May 1; 196(1_Supplement):117.1-117.1.  View on PubMed
  18. Anthony L. DeFranco. Signaling Pathways Downstream of TLRs and IL-1 Family Receptors. Encyclopedia of Immunobiology. 2016 Jan 1; 106-114.  View on PubMed
  19. Anthony L DeFranco. B Lymphocytes: Receptors. eLS. 2015 Nov 16; 1-15.  View on PubMed
  20. Beck-Engeser GB, Winkelmann R, Wheeler ML, Shansab M, Yu P, Wünsche S, Walchhütter A, Metzner M, Vettermann C, Eilat D, DeFranco A, Jäck HM, Wabl M. APOBEC3 enzymes restrict marginal zone B cells. Eur J Immunol. 2015 Mar; 45(3):695-704.  View on PubMed

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