Increased Autoreactivity and Maturity of EBI2+ Antibody-secreting Cells from Nasal Polyps

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2024 Sep 10

PMID 39253973

Authors

Junqin Bai

Atsushi Kato

Kathryn E Hulse

Joshua B Wechsler

Vikram Gujar

Julie A Poposki

Regan Harmon

Naruhito Iwasaki

Bao-Feng Wang

Julia H Huang

Whitney W Stevens

David B Conley

Kevin C Welch

Robert C Kern

Anju T Peters

Stephanie C Eisenbarth

Robert P Schleimer

Bruce K Tan

Affiliations

Soon will be listed here.

Abstract

Elevated numbers of antibody-secreting cells (ASCs) and anti-double-stranded DNA (anti-dsDNA) antibodies are found in nasal polyp (NP) tissue. The presence of anti-dsDNA IgG in tissue prospectively predicts recurrent NP but the characteristics of the source ASCs are unknown. Here, we investigated whether NP B cells expressing the extrafollicular marker EBI2 have increased propensity for autoantibody production and evaluated the molecular characteristics of NP ASCs. NPs showed increased frequencies of anti-dsDNA IgG and total IgG ASCs compared with tonsils, with more pronounced differences among EBI2+ cells. In NPs, EBI2+ cells were frequently double negative (IgD-CD27-) and ASCs. Single-cell RNA-Seq analysis of tonsils and NPs revealed substantial differences in B lineage composition, including differences in percentages of ASCs, germinal centers, proliferative cells, and non-ASCs. NPs exhibited higher expression of specific isotypes (IGHE, IGHA1, IGHA2, and IGHG4) and mature plasma genes, including SDC1 and XBP1, than tonsils. Gene Ontology biological processes indicated upregulated NF-κB and downregulated apoptosis pathways in NP ASCs. Together, these data indicate that NP EBI2+ ASCs secret increased total and anti-dsDNA IgG compared with those from tonsils and had molecular features of mature plasma cell differentiation.

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