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

人类花生过敏中胃肠道 IgE+ B 细胞的起源和克隆汇聚

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作者:Ramona A Hoh, Shilpa A Joshi, Ji-Yeun Lee, Brock A Martin, Sushama Varma, Shirley Kwok, Sandra C A Nielsen, Parastu Nejad, Emily Haraguchi, Priya S Dixit, Swetha V Shutthanandan, Krishna M Roskin, Wenming Zhang, Dana Tupa, Bryan J Bunning, Monali Manohar, Robert Tibshirani, Nielsen Q Fernandez-Becke

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.

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