The memory of pathogenic IgE is contained within CD23 + IgG1 + memory B cells poised to switch to IgE in food allergy

Abstract

Food allergy is caused by allergen-specific IgE antibodies but little is known about the B cell memory of persistent IgE responses. Here we describe in human pediatric peanut allergy CD23 ⁺ IgG1 ⁺ memory B cells arising in type 2 responses that contain peanut specific clones and generate IgE cells on activation. These 'type2-marked' IgG1 ⁺ memory B cells differentially express IL-4/IL-13 regulated genes FCER2 / CD23, IL4R , and germline IGHE and carry highly mutated B cell receptors (BCRs). Further, high affinity memory B cells specific for the main peanut allergen Ara h 2 mapped to the population of 'type2-marked' IgG1 ⁺ memory B cells and included convergent BCRs across different individuals. Our findings indicate that CD23 ⁺ IgG1 ⁺ memory B cells transcribing germline IGHE are a unique memory population containing precursors of pathogenic IgE.

One-sentence summary: We describe a unique population of IgG ⁺ memory B cells poised to switch to IgE that contains high affinity allergen-specific clones in peanut allergy.