Commensal microbiota and food antigens are important factors in the regulation of IgE production in mice (MUC4P.848)

Abstract

Abstract IgE is one of key modulators in the pathogenesis of allergy by inducing FcR-mediated activation of mast cells and basophils. Production of IgE is regulated by commensal microbiota, as it is normally undetectable in conventional mice, but highly elevated in germ-free mice shortly after weaning into solid food. The mechanism behind IgE production in germ-free mice is poorly understood, but could be a consequence of dysregulated immune responses to Ags in the food. To address this idea, germ-free mouse pups were weaned into an antigen-free elemental diet comprised of essential amino acids, vitamins and minerals. Strikingly, neither these mice nor their offsprings, designated as antigen-free mice, possessed detectable levels of serum IgE. Moreover, feeding adult germ-free mice with antigen-free diet reduced the serum IgE level, indicating continued presence of food is required to sustain high amount of IgE production. As expected, antigen-free mice weaned into normal solid food diet produced high levels of IgE. To determine the age-dependency of commensal microbiota in IgE production, germ-free mice were conventionalized at various ages, starting from 4 wks. Colonization of commensal microbiota at 4 wks of age prevented high levels of serum IgE, but not for older mice. These results suggest that food Ags by default induce a strong IgE response that is suppressed by the commensal microbiota.