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

Available for download on Thursday, April 21, 2022

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