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

Abstract

The skin is a major immune organ and skin barrier dysfunction is a major risk factor for the development of the inappropriate immune response seen in allergic disease. Skin barrier disruption alters the landscape of antigens experienced by the immune system and the downstream impacts on the antibody repertoire remain poorly characterized, particularly for the IgE isotype responsible for allergic specificity and in early life, when allergic disease is developing. In this study, we sequenced antibody gene repertoires from a large and well-characterized cohort of children with atopic dermatitis and found that food sensitization was associated with lower mutation frequencies in the IgE compartment. This trend was abrogated in children living with pets during the first year of life. These results elucidate potential molecular mechanisms underlying the protective effects of pet ownership and non-antiseptic environs reported for allergic disease, and the hygiene hypothesis more broadly. We also observed increased IgE diversity and increased isotype-switching to the IgE isotype, suggesting that B cell development, particularly isotype-switching, is heavily altered in the those with food allergen sensitizations relative to those without food allergen sensitizations. Unlike for food antigens, aeroallergen sensitization exhibited no effect on IgE mutation or diversity. Consistent patterns of antibody rearrangement were associated with food allergen sensitization in subjects with atopic dermatitis. Thus, we propose the Immune Repertoire in Atopic Disease (IRAD) score, to quantify this repertoire shift and to aid clinically in patient diagnosis and risk stratification.

Defining the T cell transcriptional landscape in pediatric liver transplant rejection at single cell resolution

“…Similar to the TCR analysis, processing of the B cell (BCR) data from the Cell Ranger pipeline was done both individually for sample-level information and as an integrated analysis to incorporate into the existing GEX Seurat object. Further, additional analysis of the immunophenotyping data for B cells was performed as described in Gill et al (77), which broadly validated the Cell Ranger values for clone size and added hypermutation scores for each cell. These recalculated values were used for all downstream analyses.…”