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

Area of Science:

• Immunology
• Genetics
• Allergy Research

Background:

• Immunoglobulin E (IgE) antibodies are crucial for defense against parasites but implicated in severe allergic reactions.
• The cells producing IgE antibodies remain poorly understood, hindering research into allergy mechanisms.

Purpose of the Study:

• To investigate the unique gene expression and splicing patterns of single IgE B cells.
• To understand the molecular basis of IgE antibody function in allergic individuals.

Main Methods:

• Isolation of single IgE B cells from patients with food allergies.
• Single-cell RNA sequencing to analyze gene expression and splicing.

Main Results:

• Identification of convergent evolution in IgE antibody gene rearrangements among unrelated individuals.
• Demonstration of acquired high affinity and cross-reactivity to peanut allergens (Ara h 2 and Ara h 3) through variable region mutations.

Conclusions:

• IgE B cell transcriptomics reveal unique molecular signatures.
• Convergent evolution shapes IgE antibody responses, contributing to allergen cross-reactivity and high affinity.