Neutrophils utilize immunoglobulins (Igs) to clear antigen, but their role in Ig production is unknown. Here we identified neutrophils in the marginal zone (MZ) of the spleen, a B cell area specialized in Ig responses to T-independent (TI) antigens. Neutrophils colonized the MZ in the absence of infection or inflammation and acquired B-helper function after receiving reprogramming signals from IL-10, an immunoregulatory cytokine released by splenic sinusoidal endothelial cells in response to microbial products. B-helper neutrophils induced Ig somatic hypermutation, class switching and production by interacting with MZ B cells through the cytokines B cell-activating factor of the TNF family (BAFF), a proliferation-inducing ligand (APRIL) and interleukin-21 (IL-21). Neutropenic patients had fewer and hypomutated MZ B cells that produced less Igs to TI antigens, which indicates that neutrophils orchestrate an innate program for adaptive humoral defense. Harnessing this pathway with neutrophil-targeting adjuvants might enhance vaccine-induced Ig responses to poorly immunogenic TI antigens, including viral glycoproteins.
(C) 2012 Lippincott Williams & Wilkins, Inc.