Fig. 4: Analysis of the circulating B cell populations in healthy donors (HD), patients with newly diagnosed (ND) and relapsed/refractory (R/R) cHL.

a Annotated UMAP of B cell clusters (n = 55,598 cells). Each cluster is labeled with a distinct color and unique number. b Feature plots of selected cell lineage and differentiation markers. c Dot plot with relative expression of selected genes in B cell clusters. Displayed genes were curated from the top differentially expressed genes that defined clusters using a two-sided Wilcoxon rank sum test, adjusted for multiple comparisons (adj p < 0.05, fold change >1.75) and supplemented with relevant markers based on a priori knowledge. The size of the dot indicates the percentage of marker-expressing cells in each cluster and the z-score reflects mean marker expression across the clusters. d Relative abundance of B cell clusters in HD (n = 13) and patients with ND cHL (n = 11). e Relative abundance of B cell clusters in patients with R/R cHL at baseline [C1D1] (n = 20) and C4D1 (n = 20), stratified by BOR to PD-1 blockade, CR (n = 9), PR (n = 5), PD (n = 6). f Number of total BCRs (left panel), number of unique BCRs (middle panel) and BCR repertoire diversity, as determined by Chao1 diversity index (right panel) in all B cells from HD (n = 13) and patients with ND cHL (n = 10) and R/R cHL at baseline [C1D1] (n = 20) and C4D1 (n = 20) stratified by BOR to PD-1 blockade. CR Complete response (n = 9), PR=partial response (n = 5), PD progressive disease (n = 6). d–f Differences between HD and patients with ND cHL were assessed by the two-sided Wilcoxon rank-sum test. The one-sided Cuzick trend test was used to compare patients with R/R cHL by response (CRs, PRs and PDs). d, e Nominal p values that were significant (p < 0.05) are listed and those that remained significant after Benjamini–Hochberg correction FDR < 0.1 are noted (*). In f p values are nominal with no Benjamini–Hochberg correction. e, f All box plots generated in R display the 25th and 75th percentiles (lower and upper hinges), median values, and whiskers. The whiskers extend from the hinges to the largest/smallest values within 1.5 times the interquartile range (IQR) from the hinge. Data points beyond the end of the whiskers are plotted individually. Source data are provided as a Source Data file.