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

Peanut-allergic patient GI tissues implicate local IgE class-switching and common IgH genetic rearrangements in pathogenesis. Peanuts in the gut Peanut allergy affects millions of children and adults worldwide, and peripheral blood IgE+ B cells have been studied in previous peanut allergy studies. Less is known about B cells in tissues exposed to peanuts, and Hoh et al. have now characterized IgE+ B cell clones in the blood, esophagus, stomach, and duodenum in 19 peanut-allergic patients. The stomach and duodenum were enriched for IgE+ B cells with a plasma cell phenotype in allergic patients. High-throughput DNA analysis indicated that tissues were the sites of local isotype switching, and similar antibody sequences for the Ara h 2 peanut allergen were shared between patients. These data better define a role for IgE+ B cells in the gastrointestinal tract in peanut allergy. 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.