Abstract

Vaccination is a method of safely generating highly specific, long-lived immunological memory that can protect a host upon future exposures to a pathogen. Memory B cells (MBCs) and high-affinity plasma cells (PCs) are pivotal populations generated during vaccine-induced immune responses as they provide rapid secondary immune responses upon antigen re-exposure. MBCs and PCs can both be produced by germinal centers (GCs), which are microanatomical structures where B cells undergo iterative rounds of somatic hypermutation and affinity-based selection. Regulation of the GC is complex and the network of factors that controls the identity, function, and magnitude of the GC B cell response continues to expand. GC B cell differentiation is associated with extensive changes in chromatin architecture and thus, chromatin remodelers have emerged as dynamic regulators of GC B cell function and maintenance. Identification and categorization of new regulatory factors in GC B cells, such as chromatin remodelers, is essential for our understanding of B cell biology and vaccine-induced GC B cell responses. mRNA-lipid nanoparticle (LNP) vaccines are a powerful technology capable of inducing robust B cell responses in both humans and mice. In mice, mRNA-LNP vaccines have the potential to be a useful tool in generating vaccine-induced populations of interest, such as GC B cells, that can be modulated in functional B cell biology studies. Herein, I characterize the magnitude and kinetics of the B cell response following mRNA-LNP vaccination in C57BL/6J mice. I leverage this platform to demonstrate that the core component of the nucleosome remodeling factor (NURF) chromatin remodeling complex, bromodomain PHD finger transcription factor (BPTF), is essential for robust B cell responses following vaccination. I utilize an Ighg1-driven Cre conditional knockout model to demonstrate that Bptf loss leads to lower magnitude populations of activated B cells, plasmablasts, GC B cells, MBCs, and PCs. Within the GC B cell compartment, the loss of Bptf was associated with a transcriptional shift away GC B cell programing and pathways associated with proliferation towards a stress-like profile. However, despite a known association between BPTF and proliferation, I did not observe a decrease in the frequency of the BPTF-deficient dark zone GC B cells in the S phase of the cell cycle, nor do I find evidence that these cells differentiate into other functional populations. Rather, I demonstrate that BPTF-deficient GC B cells, along with BPTF-deficient plasmablasts and activated B cells, are prone to cell death. Cumulatively, the data presented here demonstrate that mRNA-LNP vaccines are capable of producing robust and long-lasting B cell responses and that these responses require BPTF. This work contributes to our growing appreciation of the significance of chromatin remodeling in activated B cells and the role of BPTF in the maintenance of non-cancerous cell types.

Committee Chair

Ali Ellebedy

Committee Members

Brian Laidlaw; Jeffrey Bednarski; S. Celeste Morley; Steven Van Dyken

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Immunology)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

4-24-2026

Language

English (en)

Author's ORCID

https://orcid.org/0000-0001-6548-5086

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Available for download on Thursday, October 22, 2026

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