IgG4⁺ plasma cell enrichment and {lambda}-chain-biased BCR remodeling drive low-grade autoimmunity in chronic obstructive pulmonary disease

Authors

Duan, L., Zhao, H., Ren, X., Long, H., Li, L., Mu, M., Liu, Z., Li, K., Liu, J., Dou, Y., Cui, Y., Chen, Y., Lv, Z., Corrigan, C., Johnston, S. L., Wang, W., Yuan, H., Sun, Y.

Abstract

Background: This study aimed to elucidate B cell subset pathology in COPD, a poorly characterized area, with a focus on its similarities to and differences from classical autoimmune disorders. Methods: Single-cell RNA-sequencing (scRNA-seq) data from COPD and autoimmune diseases were obtained from the Gene Expression Omnibus (GEO) for comparative analyses of B cell subsets and functions via differentially expressed genes (DEGs), KEGG, protein-protein interaction (PPI), and cell-cell communication analyses. Serum IgG4 was measured by ELISA and correlated with clinical parameters. Peripheral blood B cells were sorted by flow cytometry for single-cell B cell receptor (BCR) sequencing. A v-Abl-Bcl2 pro-B cell line was stimulated with cigarette smoke extract (CSE) to assess abnormal development in vitro. Results: In lung tissue, IgG4 plasma cells were enriched and expressed BCR activation and inflammatory genes and TNF-NF-kB-MAPK pathways. Serum IgG4 concentrations correlated negatively with pre- and post-bronchodilator FEV1-FVC. B cells interacted with monocytes, macrophages, fibroblasts, and endothelial cells via IL-1B-IL-6, integrin, and chemokine signaling, contributing to chronic inflammation and remodeling. In peripheral blood, transitional T1 B cells were increased, accompanied by lambda-chain enrichment and increased IGLV1-47 usage, as well as enrichment of autoimmune pathways. In the bone marrow, the numbers of pre-B I cells were increased while those of small pre-B III cells were reduced, with altered expression of BCR development genes. CSE stimulation of the pro-B cell line reduced lambda expression in a concentration-dependent manner. Conclusions: The autoimmune abnormalities in COPD appear more restricted, although IgG4 antibody generation may contribute to immune-mediated lung damage.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 01 Jul 2026.

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