B cell repertoire in children with skin barrier dysfunction supports altered IgE maturation associated with allergic food sensitization

Abstract

IgE B cells produce antibodies responsible for the inappropriate specificity seen in allergic disease. In this study, we sequence antibody gene repertoires from a large, well-characterized early life cohort at risk for developing food allergy. We found that food allergen sensitization was associated with lower IgE mutation frequencies that was abrogated in children living with a pet dog, suggesting potential molecular mechanisms underlying the hygiene hypothesis (i.e., protective effects of pet ownership and non-antiseptic environs reported for allergic disease). We also observed increased IgE diversity and increased isotype-switching to IgE, suggesting that B cell development is altered in those with food allergen sensitizations relative to those without. IgE diversity was even more extreme in subjects who were highly likely to be peanut allergic. Unlike food antigen sensitization, we detected no effect of aeroallergen sensitization on IgE mutation levels and diversity. Consistent patterns of antibody rearrangement were associated with food allergen sensitization. These results have important implications for the allergic response driven by mast cells and basophils and the underlying drivers of the atopic march.