Liana Kramer
BME PhD Defense Presentation

Date: 2024-03-25
Time: 2:00 PM - 4:00 PM

Location / Meeting Link: IBB Suddath Seminar Room 1128/https://gatech.zoom.us/j/96311318574  

Committee Members:
Dr. Krishnendu Roy (Advisor); Dr. Ankur Singh (Co-Advisor); Dr. Andres Garcia; Dr. Ahmet Coskun; Dr. Leslie Chan; Dr. Frances Eun-Hyung Lee


Title: In vitro culture systems for studying the key signaling requirements of the germinal center and bone marrow for antigen-specific B cell generation and longevity

Abstract:
Memory and plasma B cells, which are responsible for maintaining protective levels of antibodies in the serum, are generated following antigen exposure. Due to the crucial roles that B cells play in the immune system, understanding and controlling the function of B cells is important in the context of therapeutic development for vaccines, immunotherapies, and cell therapies. An obstacle to producing prophylactic or therapeutic plasma and memory B cells-based treatments is a poor understanding of the complex cues and microenvironments that lead to the robust expansion of high-affinity, antigen-specific B cells and the development of long-lived plasma cells. Mimicking this complex set of events needed for B cell activation in robust and controllable in vitro platforms could allow for a better understanding of the critical signals that are necessary to mature and maintain B cells. The objectives of this work are to 1) mimic the germinal center (GC) reaction using a biomaterials particle-based platform to mediate antigen-specific B cell activation and 2) model the maturation, maintenance, and dynamics of antibody secreting cells (ASCs) within a supportive bone marrow-on-a-chip microniche. In Aim 1, we present a particle-based in vitro GC that induces rapid B cell proliferation, efficient induction of the GC reaction, and IgG class-switching in both murine and human cells. We demonstrate the importance of antigen-presentation on lipid membranes using liposomes to mimic follicular dendritic cell membrane fragments. In Aim 2, we present a microphyisological human bone marrow model that allows for ASC maturation and use it to study the dynamics and interactions of ASCs with cellular and extracellular matrix components of the bone marrow niche. These results can be leveraged to more effectively generate long-lived, high-affinity memory cell populations and to design strategies to treat conditions where B cell processes are comprised, such as aging, cancers, and autoimmunity.