Fig. 3: Comprehensive profiling of B and plasma cell subpopulations in SjD.

a The UMAP displays B/plasma cell subsets in salivary glands. b Expression levels of markers across B/plasma cell subsets. c Clonal expansion of B/plasma cells. d BCR repertoire diversity by cell clusters, with the left plot quantifying diversity scores and the right plot depicting connectivity diagrams of BCR clonotypes for different B/plasma cell subsets. Plasmablasts were excluded from the analysis due to their low abundance. Data are presented as mean values ± standard deviation (SD) derived from 200 bootstrap replicates for each group. e Subtype analysis of top 20 expanded clones in B/plasma cells across different SjD autoantibody profiles. f BCR repertoire diversity as a smooth function (D) of a single parameter q by autoantibody status. The right plot focuses on the diversity at a specific parameter (q = 4), comparing SjD with Sicca conditions. Data are presented as mean values ± SD derived from 200 bootstrap replicates for each group. g Differentially expressed gene (DEG) analysis in memory and plasma cells (Plasma and NR4A1⁺NFKB⁺ plasma) across SjD subgroups compared to Sicca using the Wilcoxon rank-sum test (two-sided). Volcano plots show log₂ fold changes (logFC) (x-axis) and –log₁₀ adjusted p-values (y-axis) for DEGs between each SjD subgroup and Sicca controls in memory (left three panels) and plasma cells (right three panels). Upregulated genes (red) and downregulated genes (blue) are highlighted with selected key genes annotated. Genes not reaching significance are shown in grey. h Differential abundance profiles of B/plasma cell populations in SjD subtypes. Beeswarm plots showing the distribution of logFC in neighborhoods in different cell type clusters in B/plasma cells. Each plot compares the abundance in SjD overall, SSA+, CENT+, and SSA + CENT+ subtypes versus Sicca or each other. Significant changes (false discovery rate (FDR) < 0.05) are highlighted, indicating enriched in each case. i The schematic diagram on the left illustrates the strategy for investigating antibody responses to SjD-related antigens. Antibodies are generated from the largest B cell lineage trees per participant (maximum 5). Their responses to each antigen (Ro60, Ro52 and centromere) were analyzed by flow cytometry. The right bar graph shows the antigens associated with the largest trees per sample. The y-axis represents the proportion of cells in the total B/plasma cells per sample and the x-axis represents the participants analyzed. Created in BioRender. Inamo, J. (2025) https://BioRender.com/kz9vcu3. Source data are provided as a Source Data file.