IgG4 expressing plasma cells and altered B cell receptor light chain usage in chronic obstructive pulmonary disease

Abstract Background This study explored B-cell heterogeneity and receptor repertoire features in chronic obstructive pulmonary disease (COPD) and examined their descriptive relationship to immune signatures reported in autoimmune diseases. Methods Public single-cell RNA-sequencing datasets from human lung and blood and murine blood and bone marrow were analysed separately by species and tissue to characterise B-cell subsets using differential gene expression, pathway enrichment, protein–protein interaction and cell–cell communication analyses. Serum immunoglobulin G4 (IgG4) was measured by enzyme-linked immunosorbent assay and correlated with clinical parameters in 35 patients with COPD. Peripheral blood B cells were sorted for single-cell B-cell receptor (BCR) sequencing; samples from three patients with COPD and four controls were pooled separately by group. A murine v-Abl/Bcl2 pro-B cell line was exposed to cigarette smoke extract (CSE) to assess developmental gene expression in vitro. Results An IGHG4-expressing cluster annotated as plasma cells was detected in the aggregated COPD lung dataset but not in the sampled controls. Serum IgG4 showed exploratory inverse associations with pre- and post-bronchodilator FEV1/FVC (the ratio of forced expiratory volume in 1 s to forced vital capacity). Ligand–receptor analysis predicted candidate interactions involving pulmonary B cells. The small human BCR cohort showed higher pooled λ-chain usage and IGLV1-47 representation. In cigarette smoke exposed mice, pooled blood and bone marrow profiles showed differences in transitional and precursor B-cell composition. CSE exposure reduced the reported λ5 expression readout in the cell line. Conclusions These exploratory findings describe B-cell dysregulation in COPD patients and smoke-exposure models. They do not establish autoreactivity, a causal role for IgG4 or a mechanistic link between λ5 suppression and mature λ-chain usage.