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 - Funding Information:
We thank Juan Lafaille for critically reading the manuscript. We thank members of the Human Immune Monitoring Center, Genomics, and Flow Cytometry Cores at ISMMS. C.J.A. received a postdoctoral fellowship from the Fundación Ramón Areces, Spain. S.P.S was a recipient of the NYU Bernard Levine postdoctoral fellowship. S.G. was supported by grants CA224319, DK124165, and CA196521. S.G. reports research funding from Bristol‐Myers Squibb, Genentech, Boehringer‐Ingelheim, EMD Serono, Takeda, and Regeneron. Work in the M.A.C.L. laboratory was supported by NIH grants R21AI133076, R01AI151707, and R01AI153708.
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 -