Lymphocyte-derived cholinergic circuits modulate germinal center output and B cell activation

Area of Science:

• Immunology
• Neuroscience
• Molecular Biology

Background:

• Germinal centers (GCs) are crucial for high-affinity antibody production.
• T cells expressing choline acetyltransferase (ChAT) are known to influence GC responses.
• The role of B cells and cholinergic signaling within GCs remains largely unexplored.

Purpose of the Study:

• To investigate whether B cells in GCs express ChAT.
• To elucidate the role of cholinergic signaling in GC B cell selection.
• To understand how acetylcholine (ACh) affects B cell fate decisions and antibody affinity.

Main Methods:

• Analysis of Chat expression in GC B cells.
• Identification of transcriptional regulators of Chat.
• In vitro studies on AChR expression and function during B cell activation.
• Assessment of ACh effects on plasma cell differentiation and BCR signaling.

Main Results:

• Chat is expressed by GC B cells, contributing to early high-affinity B cell accumulation.
• Key transcriptional regulators of Chat in GC B cells were identified.
• ACh binding to muscarinic AChRs limits plasma cell differentiation.
• ACh dampens BCR signal transduction, fine-tuning selection thresholds.

Conclusions:

• B cells utilize cholinergic signaling early in GC selection.
• ACh signaling regulates B cell fate decisions and antibody affinity.
• This reveals a novel regulatory axis impacting humoral immunity.