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

Previous work has shown that T cells expressing choline acetyltransferase (ChAT), the enzyme that synthesizes acetylcholine (ACh), are linked to the production of high-affinity antibodies in the GC response. However, whether B cells in the GC also express ChAT, and the details of the interplay of cholinergic circuits within the GC, remain unclear.

Here, we show that ChAT expressed by GC B cells contributes to the early accumulation of high-affinity GC B cells following antigen encounter. We identify key transcriptional regulators of ChAT expression in GC B cells, and demonstrate that ACh receptor (AChR) expression is dynamically coordinated during B cell activation. In vitro, we show that ACh binding to muscarinic AChRs limits plasma cell differentiation and dampens BCR signal transduction to fine-tune the threshold for affinity-based positive selection.