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

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-Becker; Neeraja Kambham; Robert B West; Robert G Hamilton; Mindy Tsai; Stephen J Galli; Rebecca S Chinthrajah; Kari C Nadeau; Scott D Boyd

doi:10.1126/sciimmunol.aay4209

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

Sci Immunol. 2020 Mar 6;5(45):eaay4209. doi: 10.1126/sciimmunol.aay4209.

Authors

Ramona A Hoh¹, Shilpa A Joshi¹, Ji-Yeun Lee¹, Brock A Martin¹, Sushama Varma¹, Shirley Kwok¹, Sandra C A Nielsen¹, Parastu Nejad¹, Emily Haraguchi¹, Priya S Dixit¹, Swetha V Shutthanandan¹, Krishna M Roskin^{2

3

4}, Wenming Zhang⁵, Dana Tupa⁵, Bryan J Bunning⁵, Monali Manohar⁵, Robert Tibshirani^{6

7}, Nielsen Q Fernandez-Becker⁸, Neeraja Kambham¹, Robert B West¹, Robert G Hamilton⁹, Mindy Tsai^{1

5}, Stephen J Galli^{1

5

10}, Rebecca S Chinthrajah^{5

11}, Kari C Nadeau^{5

11}, Scott D Boyd^{12

5}

Affiliations

¹ Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
² Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA.
³ Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
⁴ Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
⁵ Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁶ Department of Biomedical Data Sciences, Stanford University, Stanford, CA 94305, USA.
⁷ Department of Statistics, Stanford University, Stanford, CA 94305, USA.
⁸ Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁹ Division of Allergy and Clinical Immunology, Department of Medicine, and Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
¹⁰ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
¹¹ Division of Pulmonary, Allergy and Critical Care Medicine and Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, CA 94305, USA.
¹² Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

2S Albumins, Plant / immunology*
Adult
Antigens, Plant / immunology*
B-Lymphocytes / immunology*
Female
Gastrointestinal Tract / immunology*
High-Throughput Nucleotide Sequencing
Humans
Immobilized Nucleic Acids / analysis
Immobilized Nucleic Acids / immunology
Immunoglobulin E / immunology*
Male
Middle Aged
Peanut Hypersensitivity / immunology*

Substances

2S Albumins, Plant
Antigens, Plant
Ara h 2 allergen, Arachis hypogaea
Immobilized Nucleic Acids
Immunoglobulin E

Abstract

Publication types

MeSH terms

Substances

Grants and funding