Date of Award

Spring 2026

Abstract

Class switch recombination (CSR) enables B cells to generate antibodies with diverse effector functions through recombination at the immunoglobulin heavy chain (IGH) locus. This process requires coordinated transcriptional activation and DNA repair, yet its regulation remains incompletely defined. The transcription factor GLI2, a mediator of Hedgehog signaling, has been implicated in transcriptional control, but its role in CSR and IGH regulation is not well understood. To investigate the contribution of GLI2 to CSR, splenocytes from WT and hematopoietic-specific Gli2-deficient (H-Gli2-/-) mice were stimulated ex-vivo to induce switching to IgG1. Analysis of germline transcription, DNA repair enzyme expression, and post-switch transcripts revealed modest, time-dependent differences in the absence of Gli2, including altered expression of base excision repair components. However, functional CSR outcomes, including productive antibody transcripts and surface immunoglobulin, expression were not significantly affected, whereas antibody secretion was significantly altered, suggesting that GLI2 is not required for CSR completion but may regulate downstream antibody production. To examine GLI2-mediated regulation at the human IGH locus, Waldenström macroglobulinemia (WM) cell lines were used. Luciferase reporter assays containing the VDJ-Sµ intronic region demonstrated cell line-dependent effects of GLI2 on transcriptional activity. Additional analyses revealed variability in GLI2 isoform expression, suggesting that differential processing may contribute to its regulatory effects in this cancer model. While not essential for CSR, GLI2 may influence early transcriptional and DNA repair processes and contribute to locus-specific regulatory activity in human B cell malignancies.

Document Type

Master's Thesis

First Advisor

Sherine Elsawa

Second Advisor

Xuanmao Chen

Third Advisor

Vicki Jeffers

Degree Name

Master of Science

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