Author ORCID Identifier
https://orcid.org/0000-0003-4212-2260
Date of Graduation
5-2021
Document Type
Thesis (MS)
Program Affiliation
Immunology
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Katayoun Rezvani, M.D. Ph.D.
Committee Member
Richard Eric Davis, M.D.
Committee Member
Vahid Afshar-Khargan, M.D.
Committee Member
Michael Green, Ph.D.
Committee Member
Vidya Gopalakrishnan, Ph.D.
Abstract
B cells can be divided into effector and regulatory immune cells. While effector B cells are key drivers of humoral immunity due to their ability to generate antibodies specific to pathogens, regulatory B cells (Bregs) have recently been shown to control inflammatory responses in multiple diseases through the production of anti-inflammatory cytokines, including interleukin (IL)-10, IL-35 and transforming growth factor-beta (TGF-b). Ex vivo expansion of B cells has been challenging due to their tendency to undergo apoptosis in culture. Thus, creating a successful expansion protocol with exceptional viability will open the door for B cells to be used directly for adoptive therapy or as a source of antibody production ex vivo. Furthermore, a strategy to preferentially expand Bregs may be an attractive approach to mitigate autoimmune disorders and graft-versus-host disease. The primary goal of this thesis project is to understand factors that skew B cell function and to develop a protocol for the expansion of Bregs with immunomodulatory properties for cell therapy. We hypothesized that using genetic engineering tools we can skew the function of B cells toward a suppressive phenotype and support their ex vivo proliferation and survival to generate a viable subset of Bregs for cell therapy. We successfully generated B cells that displayed suppressive capabilities and used mass cytometry to characterize their phenotype. However, the immunoregulatory function of B cells was transient. Interrogation of the expanded B cells at the single cell level revealed multiple markers that could potentially be modified to maintain the suppressive capacity of the in vitro expanded B cells for future cell therapy application
Keywords
b cells, Immunotherapy, Regulatory B cells, T cells, Bregs, CytoF, cell therapy