Antibodies generated against conserved antigens suppress allergic airway disease (125.13)

Abstract

Abstract There has been a sharp rise in allergic asthma and asthma-related deaths in the developed world. The hygiene hypothesis proposes that excessively sanitary conditions early in life result in autoimmune and allergic phenomena because of a failure of the immune system to receive proper microbial stimulation during development. Chitin, a biopolymer of N-acetyl glucosamine (GlcNAc), is produced by many allergen-bearing organisms including: fungi, the exoskeleton of insects, crabs, shrimp and parasitic nematodes. We demonstrate that antibodies generated against chitin and other conserved bacterial polysaccharides, induced by neonatal vaccination or passive transfer, are reactive with and dampen the immune response against chitin and Aspergillus fumigatus. In the presence of anti-polysaccharide antibodies, we observed a marked reduction in antigen uptake, cell influx, cellular activation, and cytokine production, resulting in a striking decrease in the severity of allergic airway disease in mice. Our results suggest that antigen exposure, during the neonatal period, from environmental sources, self-antigens, or vaccination, have dramatic effects on the adult B cell repertoire and subsequent antibody responses, modulating the immune response to potential allergens later in life and thus dampening development of allergic airway disease. We propose an adjunct hypothesis that antibodies may contribute to the mechanism of protection proposed by the hygiene hypothesis.