期刊
ALLERGY
卷 78, 期 3, 页码 752-766出版社
WILEY
DOI: 10.1111/all.15601
关键词
atopic diseases; high-dimensional flow cytometry; IgE; memory IgG; single-cell sequencing
This study identified a population of IgG memory B cells in individuals with atopic diseases that expressed genes regulated by IL-4/IL-13. These cells may serve as precursors of pathogenic IgE plasma cells. The frequency of CD23(+)IL4R(+)IgG(+) memory B cells correlated with levels of circulating IgE and B cells from atopic individuals generated more IgE(+) cells in vitro.
BackgroundAtopic 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. MethodsPeripheral 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. ResultsWe 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. ConclusionsThese 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.
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