Fig. 2: Upregulation of BCR-related genes and persistent activation of naïve B cells with increased differentiation into CD21low B cells in COVID-19 CVID patients.

a UMAP visualization of B cell subpopulations, with cell numbers for CVID and non-CVID1 cohorts indicated. b Dot plot showing gene expression per B cell subpopulation; circle size denotes the percentage of expressing cells and colors indicate scaled average expression. (c) Heatmaps showing the fold change (baseline vs progression) of DEGs in CVID cohort, and non-CVID 1 cohort validated with non-CVID 2 cohort in selected B cell subsets. Genes are grouped by baseline expression comparison (equal, upregulated, or downregulated in CVID vs. non-CVID). Gene clusters are labeled on the left, and cluster sizes are indicated on the right. d Table of selected significantly enriched GO categories for clusters from (c), listing selected genes; clusters without significant enrichment are noted as NA. e Heatmaps showing fold change (baseline vs. progression/convalescence) of selected DEGs in CVID, non-CVID 1, and non-CVID 2 cohorts, showing only COVID-19 mild samples; color indicates Log2(Fold-change). f UMAP visualization of B cell clusters from spectral flow cytometry analysis. g Stacked barplot of B cell cluster frequency, calculated as cell counts per cluster over total live cells. h Box plots of selected B cell cluster frequencies. i Histograms and box plots of mean fluorescence intensity (MFI) for selected BCR-related proteins in cluster BC#7. (j) Histograms and box plots of CD95 protein levels in naïve B cells. Panels h, i, and j show biological replicates for CVID (BL: n = 3, PG: n = 4, CV: n = 4) and non-CVID controls (BL: n = 4, PG: n = 6, CV: n = 4). Two-sided t-tests were used (*p-value < 0.05). Box plot whiskers denote minimum and maximum values (excluding outliers), with the box spanning Q1 to Q3 and a horizontal line for the median. BL baseline, PG progression, CV convalescence. Source data are provided in Source Data Fig. 2 file.