Write a PREreview

Adaptive immunity in the lung must be rapidly mobilized to control bacterial pathogens, yet the neuroimmune signals that shape local B and T cell responses remain poorly defined. Here we identify a sympathetic-immune axis that regulates lung-resident memory B cells, antigen-specific IgG production, and protection against Streptococcus pneumoniae. Lung-targeted chemical sympathectomy reduced norepinephrine availability, diminished Tbet memory and resident-memory B cell populations, and markedly impaired S. pneumoniae-specific IgG, resulting in increased bacterial burden. Mice lacking Adrb1 & Adrb2-adrenergic receptors phenocopied these defects, and adoptive transfer of Adrb1/Adrb2-/- B cells into Ighm-/- hosts was sufficient to reduce IgG and worsen infection. Combined T cell depletion and B cell-intrinsic adrenergic receptor loss further impaired bacterial control and suppressed IFNgamma, indicating that norepinephrine stimulates T cell IFNgamma release and that norepinephrine and IFNgamma together drive optimal B cell IgG production. In vitro, norepinephrine enhanced T cell IFNgamma secretion, and norepinephrine plus IFNgamma synergistically increased IgG. These findings define norepinephrine as a key regulator of lung-resident humoral immunity and reveal a neuroimmune mechanism that promotes antibody-mediated bacterial clearance at the respiratory mucosa.