Origins and clonal convergence of gastrointestinal IgE ⁺ B cells in human peanut allergy

Abstract

B cells in human food allergy have been studied predominantly in the blood. Little is known about IgE⁺ B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE⁺ clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing. IgE⁺ cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell phenotype. Clonally related IgE⁺ and non-IgE-expressing cell frequencies in tissues suggest local isotype switching, including transitions between IgA and IgE isotypes. Highly similar antibody sequences specific for peanut allergen Ara h 2 are shared between patients, indicating that common immunoglobulin genetic rearrangements may contribute to pathogenesis. These data define the gastrointestinal tract as a reservoir of IgE⁺ B lineage cells in food allergy.