Science Immunology ( IF 17.6 ) Pub Date : 2020-03-06 , DOI: 10.1126/sciimmunol.aay4209 Ramona A Hoh 1 , Shilpa A Joshi 1 , Ji-Yeun Lee 1 , Brock A Martin 1 , Sushama Varma 1 , Shirley Kwok 1 , Sandra C A Nielsen 1 , Parastu Nejad 1 , Emily Haraguchi 1 , Priya S Dixit 1 , Swetha V Shutthanandan 1 , Krishna M Roskin 2, 3, 4 , Wenming Zhang 5 , Dana Tupa 5 , Bryan J Bunning 5 , Monali Manohar 5 , Robert Tibshirani 6, 7 , Nielsen Q Fernandez-Becker 8 , Neeraja Kambham 1 , Robert B West 1 , Robert G Hamilton 9 , Mindy Tsai 1, 5 , Stephen J Galli 1, 5, 10 , Rebecca S Chinthrajah 5, 11 , Kari C Nadeau 5, 11 , Scott D Boyd 1, 5
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.
中文翻译:
人花生过敏中胃肠道 IgE+ B 细胞的起源和克隆会聚。
人类食物过敏中的 B 细胞主要在血液中进行研究。对暴露于膳食抗原的组织中的 IgE + B 细胞或浆细胞知之甚少。我们使用高通量 DNA 测序对 19 名花生过敏患者的血液、胃、十二指肠和食道中的IgE +克隆进行了表征。过敏患者的IgE +细胞在胃和十二指肠中富集,并具有浆细胞表型。克隆相关 IgE +组织中不表达 IgE 的细胞频率表明局部同种型转换,包括 IgA 和 IgE 同种型之间的转换。花生过敏原 Arah 2 特异性的高度相似的抗体序列在患者之间共享,这表明常见的免疫球蛋白基因重排可能有助于发病机制。这些数据将胃肠道定义为食物过敏中 IgE + B 谱系细胞的储存库。