The role of B cell-derived acetylcholine in the regulation of antiviral immunity

Abstract

Abstract Acetylcholine (ACh) is a neurotransmitter of signals from pre to post-synaptic neurons and from neural to muscle and gland cells, requiring the enzyme choline acetyltransferase (ChAT) for production. ChAT-GFP reporter mice recently showed that ACh is produced also by B and T cells. The physiological role of B cell-derived ACh remains largely unknown. Using ChAT-GFP mice, we show that naïve, conventional (B-2) as well as B-1 cells are major contributors to ChAT expression in spleen, lymph nodes, lung and pleural cavities, with B-1 cells expressing ChAT at the highest frequencies. In contrast, naive CD4 and CD8 T cells are ChATneg. To study the function of B cell-derived ACh we first infected ChAT reporter mice with influenza A/Puerto Rico/8/34. Infection led to increased ChAT+ B-1, but not B-2 cell numbers in the lungs at 3 days post-infection and of ChAT+ CD4 T cells at day 7. ChAT+ CD4 T cells were CD44hi, while the resting CD44lo naïve CD4 and CD8 T cells remained ChATneg. Mice with a B cell-specific deletion in Chat showed changes in lung cell composition, had decreased weight loss, and significant increases in influenza-specific serum IgG1 at day 14 but not later, compared to their wild-type controls. The data suggest that B cell-derived ACh significantly affects lung inflammation during influenza A infection and regulates the size of early extrafollicular B cell responses.