High-affinity allergen-specific human antibodies cloned from single IgE B cell transcriptomes

Science. 2018 Dec 14;362(6420):1306-1309. doi: 10.1126/science.aau2599.

Abstract

Immunoglobulin E (IgE) antibodies protect against helminth infections but can also cause life-threatening allergic reactions. Despite their role in human health, the cells that produce these antibodies are rarely observed and remain enigmatic. We isolated single IgE B cells from individuals with food allergies and used single-cell RNA sequencing to elucidate the gene expression and splicing patterns unique to these cells. We identified a surprising example of convergent evolution in which IgE antibodies underwent identical gene rearrangements in unrelated individuals. Through the acquisition of variable region mutations, these IgE antibodies gained high affinity and unexpected cross-reactivity to the clinically important peanut allergens Ara h 2 and Ara h 3. These findings provide insight into IgE B cell transcriptomics and enable biochemical dissection of this antibody class.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2S Albumins, Plant / immunology
  • Allergens / immunology*
  • Antibody Affinity / genetics*
  • Antibody Affinity / immunology
  • Antigens, Plant / immunology
  • Arachis / immunology
  • Cross Reactions
  • Gene Rearrangement, B-Lymphocyte*
  • Glycoproteins / immunology
  • Humans
  • Immunoglobulin E / genetics*
  • Immunoglobulin E / immunology
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / immunology
  • Mutation
  • Peanut Hypersensitivity / immunology*
  • Plant Proteins / immunology
  • RNA Splicing
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Transcriptome

Substances

  • 2S Albumins, Plant
  • Allergens
  • Antigens, Plant
  • Ara h 2 allergen, Arachis hypogaea
  • Ara h 3 allergen, Arachis hypogea
  • Glycoproteins
  • Immunoglobulin Variable Region
  • Plant Proteins
  • Immunoglobulin E