Neutrophils recruited to immunization sites initiating vaccine-induced antibody responses by locally expressing BAFF

Neutrophils played a key role in the innate immune responses. Less is known about whether and how the neutrophils recruited in the immunization sites affecting the vaccine-induced antibody responses. In the process of evaluating the efficacy of an oil-in-water emulsion-formulated vaccine in mice, we found that neutrophils were rapidly and massively recruited to immunization sites but were barely detected in the draining lymph nodes. Interestingly, B cell-activating factor (BAFF) was abundantly expressed in the recruiting neutrophils at a very early stage. The initial neutrophil-derived BAFF firstly brought about the B cell responses in the local part, then subsequently in lymphoid organs. Activated B cells produced more BAFF through TLR9-IRF5 signaling pathway, thereby amplifying the vaccine-induced antibody responses. Suppressing BAFF in the neutrophils could weaken the B cell activation and reduce the antibody production. The data indicate that vaccines endow neutrophils with the potential to orchestrate antibody responses at immunization sites.