Fig. 4: Single-cell analysis of B lymphocytes and BCR repertoire reveal plasmablast expansion and clonality differences between genders.
From: Single-cell multi-omics analysis of the immune response in COVID-19
a, UMAP visualization of 74,019 cells in the B cell lineage identified from gene expression data. b, Dot plots of gene (top) and surface protein (bottom) expression for populations shown in a. c, Bar plot of the mean proportion of cell types shown in a. d, Proportion of total IgA and IgA2 in plasmablast and plasma cells based on BCR data. Kruskal–Wallis test with Benjamini–Hochberg correction. e, Coordinated changes between TFH and B cells assessed by differential correlation analysis (empirical P ≤ 0.1). Shown is the Pearson correlation (± bootstrap s.e.m.) between TFH proportions and plasmablast or plasma cell (combined); only significant trends are shown. f, GSEA of MSigDB hallmark signatures in naive B cells, switched memory B cells and plasmablasts for asymptomatic/symptomatic COVID-19 versus healthy groups. Size of circles indicate (absolute) normalized enrichment score (NES). GSEA (permutation) nominal P < 0.05 and FDR < 0.25 denoted by non-gray colored dots. EMT, epithelial–mesenchymal transition; UV, ultraviolet. g, Dot plots of genes related to TNF signaling and BCR signaling in naive B cells, switched memory B cells and plasmablasts. Size of circles indicates the percentage of cells expressing the gene, and color gradient corresponds to increasing mean expression value. h, Scatterplot of clonotype size by node closeness centrality gini indices with marginal histograms indicating the distribution. Each dot represents an individual. i, BCR overlap incidence plot. Nodes correspond to individual donors colored by (inner ring) severity and (outer ring) site from which samples were collected. Edges indicate if at least one cell from each individual displayed an identical combination of heavy and light-chain V and J gene usage with CDR3 similarity allowance (≥85%). j, Clonotype size (left) and node closeness centrality gini indices (right) separated by gender. Mann–Whitney U test with Benjamini–Hochberg correction between the gender groups within each severity status. Color of adjusted P values indicates the gender group with the higher mean value. The box portion of the box plots extends from the 25th to 75th percentiles, whiskers extend from the smallest to largest values, and the middle line corresponds to the median. NS, not significant.
