Origins and clonal convergence of gastrointestinal IgE+ B cells in human peanut allergy.
Ramona A HohShilpa A JoshiJi-Yeun LeeBrock A MartinSushama VarmaShirley KwokSandra C A NielsenParastu NejadEmily HaraguchiPriya S DixitSwetha V ShutthanandanKrishna M RoskinWenming ZhangDana TupaBryan J BunningMonali ManoharRobert TibshiraniNielsen Q Fernandez-BeckerNeeraja KambhamRobert B WestRobert G HamiltonMindy TsaiStephen J GalliRebecca S ChinthrajahKari Christine NadeauScott D BoydPublished in: Science immunology (2020)
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.
Keyphrases
- end stage renal disease
- induced apoptosis
- newly diagnosed
- ejection fraction
- single cell
- high throughput
- cell cycle arrest
- prognostic factors
- gene expression
- stem cells
- machine learning
- patient reported outcomes
- immune response
- cell therapy
- oxidative stress
- deep learning
- signaling pathway
- cell death
- cell proliferation
- endoplasmic reticulum stress
- copy number