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

© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:78

Enthalten in:

Allergy - 78(2023), 3 vom: 21. März, Seite 752-766

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

207137-56-2
37341-29-0
Atopic diseases
FCER2 protein, human
High-dimensional flow cytometry
IL4R protein, human
IgE
Immunoglobulin E
Immunoglobulin G
Interleukin-13
Interleukin-4
Interleukin-4 Receptor alpha Subunit
Journal Article
Lectins, C-Type
Memory IgG
Receptors, IgE
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Single-cell sequencing

Anmerkungen:

Date Completed 06.03.2023

Date Revised 23.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1111/all.15601

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM349578613