Journal Article

Increased autoreactivity and maturity of EBI2+ antibody-secreting cells from nasal polyps

Iwasaki, Naruhito, Huang, Julia H., Stevens, Whitney W., Welch, Kevin C., Kern, Robert C., Harmon, Regan, Hulse, Kathryn E., Tan, Bruce K., Bai, Junqin, Poposki, Julie A., Schleimer, Robert P., Wang, Bao-Feng, Conley, David B., Eisenbarth, Stephanie C., Wechsler, Joshua B., Gujar, Vikram, Kato, Atsushi, Peters, Anju T.

2024

Overview

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.

• Publisher: American Society for Clinical Investigation,American Society for Clinical investigation
• Subject: Adult / Aged / Anti-DNA antibodies / Antibodies / Antibodies, Antinuclear - immunology / Antibody-Producing Cells - immunology / Antibody-Producing Cells - metabolism / Antigens / Apoptosis / Autoantibodies / B-Lymphocytes - immunology / B-Lymphocytes - metabolism / CD27 antigen / Cell differentiation / Cells / Female / Flow cytometry / Germinal centers / Humans / Immunoglobulin D / Immunoglobulin G / Immunoglobulin G - immunology / Immunoglobulin G - metabolism / Immunology / Inflammation / Isotypes / Lymphocytes B / Male / Middle Aged / Minor Histocompatibility Antigens - genetics / Minor Histocompatibility Antigens - immunology / Minor Histocompatibility Antigens - metabolism / Nasal Polyps - immunology / Nasal Polyps - metabolism / Nasal Polyps - pathology / NF-κB protein / Palatine Tonsil - cytology / Palatine Tonsil - immunology / Plasma / Polyps / Tonsil / Young Adult