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

Carlos J. Aranda, Edgar Gonzalez-Kozlova, Sean P. Saunders, Weslley Fernandes-Braga, Miyo Ota, Sriram Narayanan, Jin Shu He, Ester Del Duca, Bose Swaroop, Sacha Gnjatic, Gail Shattner, Joan Reibman, Nicholas A. Soter, Emma Guttman-Yassky, Maria A. Curotto de Lafaille

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)752-766
Number of pages15
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume78
Issue number3
DOIs
StatePublished - Mar 2023

Keywords

  • IgE
  • atopic diseases
  • high-dimensional flow cytometry
  • memory IgG
  • single-cell sequencing

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