LSD1 Cooperates with Noncanonical NF-κB Signaling to Regulate Marginal Zone B Cell Development

Area of Science:

• Immunology
• Epigenetics
• Cell Biology

Background:

• Marginal zone B cells (MZB) are vital for rapid responses to blood-borne pathogens.
• While transcriptional changes in MZB development are known, the epigenetic mechanisms remain unclear.
• The role of histone demethylase LSD1 in B cell development was unexplored.

Purpose of the Study:

• To investigate the role of LSD1 in the development of B cell subsets.
• To elucidate the epigenetic mechanisms governing MZB formation.

Main Methods:

• Conditional deletion of LSD1 in mice B cells.
• Gene expression and chromatin accessibility analyses.
• Ex vivo MZB development assays.
• Protein-protein interaction studies.

Main Results:

• LSD1 deficiency reduced MZB numbers with minimal impact on other B cell populations.
• LSD1 repressed genes in MZB and regulated transcription factor motifs, including NF-κB.
• LSD1-deficient and NF-κB-inhibited cells showed impaired MZB development.
• LSD1 interacts with p52 and regulates downstream targets of noncanonical NF-κB signaling.

Conclusions:

• LSD1 is essential for proper MZB development.
• Epigenetic modulation of noncanonical NF-κB signaling by LSD1 is critical for MZB formation.
• LSD1 plays a key role in B cell immunity and response to pathogens.