IL-9 receptor signaling in memory B cells regulates humoral recall responses

Memory B cells (B-mem) are the basis of long-lasting humoral immunity. They respond to re-encountered antigens by rapidly producing specific antibodies and forming germinal centers (GCs), a recall response that has been known for decades but remains poorly understood. We found that the receptor for the cytokine IL-9 (IL-9R) was induced selectively on B-mem cells after primary immunization and that IL-9R-deficient mice exhibited a normal primary antibody response but impaired recall antibody responses, with attenuated population expansion and plasma-cell differentiation of B-mem cells. In contrast, there was augmented GC formation, possibly due to defective downregulation of the ligand for the co-stimulatory receptor ICOS on B-mem cells. A fraction of B-mem cells produced IL-9. These findings indicate that IL-9R signaling in B-mem cells regulates humoral recall responses.