Enhanced Clonality and Autoantibody Production by Antibody-Secreting Cells in CRSwNP 3002

Abstract Description Background Nasal polyps (NP) in chronic rhinosinusitis with NP (CRSwNP) contain increased extrafollicularly activated antibody-secreting cells (ASCs) that produce autoantibodies, including anti-dsDNA IgG, which predict NP recurrence post-surgery. However, the cellular profile and antigen receptor repertoire of ASCs in NP remain unclear. Methods NP, tonsil tissues, and blood were collected during surgery. ASCs, including plasmablasts (PB, CD38+CD138-) and plasma cells (PC, CD38+CD138+), as well as IgG+ plasma cells, was quantified by flow cytometry. B and T cell receptor repertoires (BCR and TCR) were assessed using clonality (mean frequency of unique CDR3 sequences) and Diversity Index 50 (DI50), representing clones making up 50% of the total repertoire. Results In NP tissue (n = 5), PB frequency was significantly lower than in tonsils (n = 6) (p < 0.05) but comparable to blood (n = 4). Conversely, PC frequency was significantly higher in NP than in blood (p < 0.05) and tonsils (p < 0.01). BCR-seq indicated increased clonality and lower DI50 in NP, and IGHV3-34, a dsDNA-reactive Ig heavy chain, while TCRβ-seq showed marginal differences. Additionally, recurrent NP exhibited a trend toward lower DI50 versus non-recurrent NP. Conclusions Extrafollicularly activated ASCs in NP tissue predominantly consist of PCs expressing the mature B cell marker CD138. B cells in NP display increased BCR clonality, particularly in recurrent NP. Funding Sources CRISP2 P01 AI145818, R01 AI134952, and R01 DC016645 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)