Skip Navigation LinksHome > April 2012 - Volume 59 - Issue > 102 A Novel Innate Pathway for Antibody Diversification and...
JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/01.qai.0000413739.45104.fa

102 A Novel Innate Pathway for Antibody Diversification and Production.

Cerutti, Andrea

Collapse Box


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.