Abstract

Project 3: Human Long-lived Plasma Cell Survival and the Role of the BM Microniche. Long-lived plasma cells (LLPC) sustain protective antibody production for a lifetime and require the bone marrow microniche to sustain survival. In our lab, we have definitively linked the long-lived viral serum antibody source to the LLPC cellular compartment within the human bone marrow (BM) (CD19-CD38hiCD138+) and developed in vitro BM microniche cultures that mimics the BM microenvironment to sustain PC survival. In this application, we will study the role of the BM microniche on LLPC generation and maintenance by (1) understanding the transcriptional and epigenetic regulation of BM LLPC, (2) understanding the LLPC fate determinants especially the BM adaptation to a hypoxic BM microenvironment and (3) elucidating the essential LLPC survival factors provided by the BM microniche. The significance of this work will be to understand the role of the BM microniche in LLPC survival for life-long antibody protection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI125180-05
Application #
9930040
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2016-06-25
Project End
2021-05-31
Budget Start
2020-06-01
Budget End
2021-05-30
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Emory University
Department
Type
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Tipton, Christopher M; Hom, Jennifer R; Fucile, Christopher F et al. (2018) Understanding B-cell activation and autoantibody repertoire selection in systemic lupus erythematosus: A B-cell immunomics approach. Immunol Rev 284:120-131
Upadhyay, Amit A; Kauffman, Robert C; Wolabaugh, Amber N et al. (2018) BALDR: a computational pipeline for paired heavy and light chain immunoglobulin reconstruction in single-cell RNA-seq data. Genome Med 10:20
Jenks, Scott A; Cashman, Kevin S; Zumaquero, Esther et al. (2018) Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus. Immunity 49:725-739.e6
Haines, Robert R; Barwick, Benjamin G; Scharer, Christopher D et al. (2018) The Histone Demethylase LSD1 Regulates B Cell Proliferation and Plasmablast Differentiation. J Immunol 201:2799-2811
Barwick, Benjamin G; Scharer, Christopher D; Martinez, Ryan J et al. (2018) B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation. Nat Commun 9:1900
Guo, Muyao; Price, Madeline J; Patterson, Dillon G et al. (2018) EZH2 Represses the B Cell Transcriptional Program and Regulates Antibody-Secreting Cell Metabolism and Antibody Production. J Immunol 200:1039-1052
Sanz, Iñaki (2017) New Perspectives in Rheumatology: May You Live in Interesting Times: Challenges and Opportunities in Lupus Research. Arthritis Rheumatol 69:1552-1559
D'Angio, Carl T; Wyman, Claire P; Misra, Ravi S et al. (2017) Plasma cell and serum antibody responses to influenza vaccine in preterm and full-term infants. Vaccine 35:5163-5171
Tanaka, Toshihiro; Zhang, Weici; Sun, Ying et al. (2017) Autoreactive monoclonal antibodies from patients with primary biliary cholangitis recognize environmental xenobiotics. Hepatology 66:885-895
Jaworski, Juan Pablo; Bryk, Peter; Brower, Zachary et al. (2017) Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Env-specific antibody response in SHIV-infected rhesus macaques. PLoS One 12:e0172524

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