Increased Autoreactivity and Maturity in EBI2+ Antibody-Secreting Cells from Nasal Polyps

Rationale: Elevated numbers of antibody secreting cells (ASCs) and anti-dsDNA antibodies are found in nasal polyp (NP) tissue. Tissue anti-dsDNA IgG prospectively predicts recurrent NP, but the characteristics of the source ASCs are unknown. Objectives: To investigate whether NP B cells expressing the extrafollicular marker EBI2 have increased propensity for autoantibody production and to evaluate the molecular characteristics of NP ASCs. Findings: NPs (n=8) showed increased frequencies of anti-dsDNA IgG and total IgG ASCs (34- and 9-fold, respectively, both p<0.0001) compared to tonsils (n=10), with more pronounced differences among EBI2+ cells. In NPs, EBI2+ cells were frequently double-negative (IgD-CD27-) and ASCs (36.3% and 19.5%, respectively). ScRNA-seq analysis of tonsils and NPs (both n=5) revealed substantial differences in B lineage composition: ASCs (1.2% vs 44.1%), germinal center (23.1% vs 0.2%), proliferative (12.6% vs 3.0%), and non-ASCs (63.1% vs 52.7%), respectively. NPs exhibited higher expression (>2-fold) of specific isotypes (IGHE, IGHA1, IGHA2, and IGHG4), and mature plasma genes including SDC1 and XBP1 than tonsils. GO biological processes indicated upregulated NF-κB and downregulated apoptosis pathways in NP ASCs. Conclusions: NP EBI2+ ASCs secreted increased total and anti-dsDNA IgG compared to those from tonsils and had molecular features of mature plasma cell differentiation.