B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis

Autonomic nerves control organ function through the sympathetic and parasympathetic branches, which have opposite effects. In the bone marrow, sympathetic (adrenergic) nerves promote hematopoiesis; however, how parasympathetic (cholinergic) signals modulate haematopoiesis is unclear. Here we show that B lymphocytes were an important source of acetylcholine, a neurotransmitter of the parasympathetic nervous system which reduced hematopoiesis. Single cell RNA sequencing identified 9 clusters of cells that expressed the acetylcholine receptor Chrna7 in the bone marrow stem cell niche, including endothelial and mesenchymal stromal cells. Deletion of B cell-derived acetylcholine resulted in the differential expression of various genes, including Cxcl12 in LepR(+) stromal cells. Pharmacologic inhibition of acetylcholine signaling increased the systemic supply of inflammatory myeloid cells in mice and patients with cardiovascular disease.