IgG memory B cells expressing IL4R and FCER2 are associated with atopic diseases. Issue 3 (19th December 2022)

• Record Type: Journal Article
• Authors: Aranda, Carlos J.; Gonzalez‐Kozlova, Edgar; Saunders, Sean P.; Fernandes‐Braga, Weslley; Ota, Miyo; Narayanan, Sriram; He, Jin‐Shu; Del Duca, Ester; Swaroop, Bose; Gnjatic, Sacha; Shattner, Gail; Reibman, Joan; Soter, Nicholas A.; Guttman‐Yassky, Emma; Curotto de Lafaille, Maria A.
• Is Part Of: Allergy. Volume 78:Issue 3(2023)
• Page Start: 752
• Page End: 766
• Publication Date: 2022-12-19
• Subjects: atopic diseases -- high‐dimensional flow cytometry -- IgE -- memory IgG -- single‐cell sequencing; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.15601
• Languages: English
• ISSNs: 0105-4538

Abstract

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. Abstract : We identified a novel population of IgG + IL4R + CD23 + type 2‐marked memory B cells that are increased in peripheral blood of subjects with asthma or atopic dermatitis compared to non‐atopic subjects. Type 2‐marked IgG memory B cell frequency correlates with circulating levels of IgE antibodies. They express IL‐4/IL‐13 regulated genes, ie FCER2 / CD23, IL4R, IL13RA1, and IGHE . B cells from atopic subjects generate more IgE cells when stimulated in ex vivo cultures than B cells from non‐atopic subjects. IgG + IL4R + CD23 + have the highest ability to switch to IgE among IgG memory B cells.Abbreviations: BAFF, B cell activating factor; CD40L, CD40 ligand; FCER2, Fc epsilon receptor II; Ig, immunoglobulin; IGH, immunoglobulin heavy constant; IL, interleukin; IL4RA, IL‐4 receptor subunit alpha; IL13RA1, IL‐13 receptor subunit alpha 1; IU/ml, international units per milliliter; scRNAseq, single cell RNA sequencing