Role of GLI2 in antibody production

The regulation of immunoglobulin heavy chain (IGH) transcription and expression is a critical component of antibody secretion by activated B cells. Despite significant advances in understanding the mechanisms driving antibody production, many of the molecular processes involved remain unclear. Dysregulation of immunoglobulin (Ig) production is a hallmark of various malignant and autoimmune disorders, highlighting the need for a deeper understanding of the transcriptional regulation of IGH and class switch recombination (CSR) to target these pathways in Ig-related pathologies. While studies on human B cells typically rely on polyclonal populations from peripheral blood or tonsil samples, these models present challenges in comprehensively studying IGH regulation. To overcome this, we are using novel monoclonal IgM-secreting B cell lines to investigate the transcriptional regulation of IGH and CSR in human cells. In this proposal, we examine a novel role for the transcription factor GLI2 as a critical checkpoint that facilitates CSR in B cells. By combining human monoclonal IgM-secreting B cell lines and conditional transgenic mouse models with Gli2 deficiency in B cells and hematopoietic cells, we aim to understand the functional role of GLI2 in B cell biology. Specifically, we hypothesize that GLI2 directly regulates IGH transcription and CSR by binding to IGH V-region promoters and V-J intron sequences (Aim 1), and indirectly modulates CSR by negatively regulating AICDA expression, thereby influencing B cell differentiation (Aim 2). Project Number: 1R15AI188249-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: Sherine Elsawa | Institution: UNIVERSITY OF NEW HAMPSHIRE, DURHAM, NH | Award Amount: $568,367 | Activity Code: R15 | Study Section: Special Emphasis Panel[ZRG1 IIDA-C (02)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R15AI18824901A1