CD23+IgG1+ memory B cells are poised to switch to pathogenic IgE production in food allergy

Food allergy is caused by allergen-specific IgE but little is known about the B cell memory of persistent responses. Here we describe in pediatric peanut allergy a population of CD23+IgG1 memory B cells that contains peanut-specific clones and generates IgE plasma cells on activation. Through single cell transcriptomics and B cell receptor (BCR) sequencing, we characterized FCER2/CD23+ IgG1 memory B cells co-expressing IL4R, IL13RA1, IGHE and carrying highly mutated BCRs. Further we found that peanut allergen (Ara h 2)-specific B cells were mostly IgG1 memory cells, carried highly mutated BCRs compared to diphtheria toxin-specific B cells, and expressed FCER2 and germlin IGHE. Our findings suggest that CD23+IgG1+ memory B cells transcribing IGHE are a unique memory population containing precursors for pathogenic IgE in food allergy. Sampling of peanut allergic (PA) and non-allergic, non-atopic (non-PA) subjects UPDATE: [09-26-2024] The following supplementary files were updated: GSE208235_bcr_gex.tsv GSE208235_data_integrated_annotated_clusters_over.rds GSE208235_filtered_sequences.tsv