IgG memory B cells expressing IL4R and FCER2 are associated with atopic diseases

Background: Atopic diseases are characterized by IgE antibody responses that are dependent on cognate CD4 T cell help and T cell-produced IL-4 and IL-13. Current models of IgE cell differentiation point to the role of IgG memory B cells as precursors of pathogenic IgE plasma cells. The goal of this work was to identify intrinsic features of memory B cells that are associated with IgE production in atopic diseases. Methods: Peripheral blood B lymphocytes were collected from individuals with physician diagnosed asthma or atopic dermatitis (AD) and from non-atopic individuals. These samples were analyzed by spectral flow cytometry, single cell RNA sequencing (scRNAseq), and in vitro activation assays. Results: We identified a novel population of IgG memory B cells characterized by the expression of IL-4/IL-13 regulated genes FCER2/CD23, IL4R, IL13RA1, and IGHE, denoting a history of differentiation during type 2 immune responses. CD23⁺IL4R⁺IgG⁺ memory B cells had increased occurrence in individuals with atopic disease. Importantly, the frequency of CD23⁺IL4R⁺IgG⁺ memory B cells correlated with levels of circulating IgE. Consistently, in vitro stimulated B cells from atopic individuals generated more IgE⁺ cells than B cells from non-atopic subjects. Conclusions: These findings suggest that CD23⁺IL4R⁺ IgG⁺ memory B cells transcribing IGHE are potential precursors of IgE plasma cells and are linked to pathogenic IgE production.