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Title page for ETD etd-06132017-140256

Type of Document Dissertation
Author Wogsland, Cara Ellen
Author's Email Address cara.wogsland@gmail.com
URN etd-06132017-140256
Title Systems Biology of Mature Human B cells in Health and Illness
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Andrew J. Link Committee Chair
Holly M. Algood Committee Member
Jonathan M. Irish Committee Member
Leslie J. Crofford Committee Member
R. Stokes Peebles Committee Member
  • tumor immunology
  • cancer
  • cell signaling
  • phospho-flow
  • tonsil
  • single cell biology
  • t-SNE
  • systems biology
  • viSNE
  • computational biology
  • immunology
  • follicular lymphoma
  • B cells
  • mass cytometry
  • flow cytometry
  • CyTOF
Date of Defense 2017-05-31
Availability unrestricted
B cells play a crucial role in adaptive immunity. They perform a multitude of functions including antibody and cytokine production and antigen presentation. The human adaptive immune response would not function effectively without B cells. The genome of a B cell undergoes profound changes during maturation and differentiation. This genome manipulation is a double-edged sword that provides both adaptive immunity to a wide array of pathogens and risks creating genomic changes associated with cancer, autoimmunity, or allergic disease. Studying B cells from a healthy immune system is important for understanding natural disease course, vaccine development, and the manufacture of antibodies for research and medicine. Here, I apply a systems biology approach to understanding B cells in health and disease with the use of mass cytometry and computational tools. The goals were to 1) Characterize B cells in follicular lymphoma (FL), 2) Characterize germinal center (GC) B cell signaling in response to reactive oxygen species (ROS), and 3) Integrate and optimize computational tools such as viSNE to capture the biology of B cells. This systems biology approach produced numerous findings. The GC B cell compartment was diminished in FL tumors compared to tonsil. FL malignant B cells displayed both intra- and inter-tumoral heterogeneity in phenotype. This heterogeneity within the malignant cells was driven by cell to cell variation in expression levels of human leukocyte antigen D related antigen (HLA-DR). FL malignant B cells, which are thought to arise from a GC B cell, were phenotypically distinct from GC B cells. GC B cells were found to be more sensitive to ROS than other B cell types found in tonsil. viSNE served as a useful tool in the visualization and characterization of malignant and non-malignant cells. The systems biology approach using mass cytometry enabled simultaneous identification and characterization of B cells in health and disease settings.
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