CD23⁺ IgG1⁺ memory B cells in food allergy as precursors of pathogenic IgE responses

Sammanfattning

Peanut allergy is a severe and often lifelong condition driven by IgE-mediated immune responses and is a major cause of food-induced anaphylaxis. Increasing evidence suggests that long-term allergic memory is maintained by specialized memory B-cell populations capable of regenerating pathogenic IgE responses. This study aimed to identify and characterize memory B-cell populations associated with persistent peanut allergy, focusing on FCER2 high type 2- associated memory B cells and their role in IgE-related immunity. To investigate this, publicly available multimodal single-cell datasets were re-analyzed, including single-cell RNA sequencing (scRNA-seq) data and B-cell receptor (BCR) repertoire data generated using 10x Genomics and PacBio sequencing. In addition, clonal lineage reconstruction and computational antibody–epitope docking analyses were performed to further characterize allergen-associated B-cell responses. Peripheral blood immune cells from peanut-allergic and non-allergic individuals were analyzed to examine transcriptional profiles, immunoglobulin isotypes, somatic hypermutation (SHM), and allergen-associated antibody features. A distinct FCER2 high memory B-cell population was identified, characterized by elevated expression of FCER2, IGHE, IL4R, IL13RA1, and HOPX, consistent with a type 2-associated memory phenotype. These cells showed high SHM frequencies, enrichment of mutated IgG isotypes, and evidence of transcriptional priming toward IgE class switching through germline IGHE expression. Integration of PacBio and 10x datasets further identified convergent allergen-associated BCR features shared across peanut-allergic donors. Together, these findings support a model in which FCER2 high IgG memory B cells act as a reservoir for persistent allergic memory and pathogenic IgE responses in peanut allergy, providing insight into food allergy mechanisms and potential future therapeutic targets.