Abstract

B cells are key components of the adaptive immune system that mediate humoral immunity through the production of antigen-specific antibodies. The generation of functional B cells involves multiple stages of differentiation across distinct anatomical niches, requiring precise regulation of microenvironmental signals and intrinsic transcriptional networks. SWI/SNF chromatin remodeling complexes have emerged as key regulators of B cell lineage commitment by modulating the accessibility of transcriptional programs required for differentiation and maturation. However, the specific roles of individual SWI/SNF subunits and distinct complexes within early B cell differentiation remain poorly understood. In this thesis, I investigated the function of Arid2, an essential subunit of the PBAF chromatin remodeling complex, in murine B cell development. Using conditional knockout models generated with Mb1-Cre and CD19-Cre mice, I demonstrate that Arid2 regulates the differentiation of progenitor B cells into mature Follicular B cells. Mb1-cre mediated deletion resulted in a more pronounced reduction of splenic and circulating Follicular B cells compared to CD19-Cre deletion, indicating that earlier loss of Arid2 disrupts B cell maturation. Transcriptomic profiling of isolated pro-B, pre-B, and Follicular B cells revealed that Arid2 regulates stage-specific gene expression programs throughout B cell development, progressively affecting lineage specification, B cell receptor signaling, and immune response pathways. Functionally, Arid2-deficient B cells exhibited intrinsic defects in T-cell dependent immune responses, including reduced germinal center formation and impaired IgG antibody production. Together, these findings define a critical function for Arid2 in early B cell differentiation and humoral immunity. Ultimately, this work advances our understanding of chromatin remodeling dynamics during B cell development and establishes a foundation for future studies of Arid2-mediated regulatory mechanisms in both normal and disease contexts.

Committee Chair

George Souroullas

Committee Members

Abby Green; Grant Challen; Jeffrey Bednarski; Laura Schuettpelz

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Molecular Genetics & Genomics)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

12-15-2025

Language

English (en)

Author's ORCID

0000-0003-4147-968X

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