TY - JOUR
T1 - IgG memory B cells expressing IL4R and FCER2 are associated with atopic diseases
AU - Aranda, Carlos J.
AU - Gonzalez-Kozlova, Edgar
AU - Saunders, Sean P.
AU - Fernandes-Braga, Weslley
AU - Ota, Miyo
AU - Narayanan, Sriram
AU - He, Jin Shu
AU - Del Duca, Ester
AU - Swaroop, Bose
AU - Gnjatic, Sacha
AU - Shattner, Gail
AU - Reibman, Joan
AU - Soter, Nicholas A.
AU - Guttman-Yassky, Emma
AU - Curotto de Lafaille, Maria A.
N1 - Publisher Copyright:
© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
KW - IgE
KW - atopic diseases
KW - high-dimensional flow cytometry
KW - memory IgG
KW - single-cell sequencing
UR - http://www.scopus.com/inward/record.url?scp=85144285994&partnerID=8YFLogxK
U2 - 10.1111/all.15601
DO - 10.1111/all.15601
M3 - Article
C2 - 36445014
AN - SCOPUS:85144285994
SN - 0105-4538
VL - 78
SP - 752
EP - 766
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
IS - 3
ER -