Fig. 3: Comparative dimensionality reduction plots identify deficiencies of specific B-cell population in toxicity patients (n = 46).

a UMAP plots stratified according to condition, “no toxicity”, “toxicity” and “healthy controls”. Clusters highlighted by blue boxes correspond to clusters 1, 2, 3, 9 and 12 identified from Fig. 2a. These clusters are attenuated in the “toxicity” cohort in this unsupervised analysis. The box labelled “A” is encircling cluster 2 (peach). The box labelled “B” is encircling clusters 1 (red) and 3 (blue). The box labelled “C” is encircling clusters 9 (pink) and 12 (light green). All samples are randomly downsampled to account for equally representative populations across samples. b Diffusion map stratified according to condition, “no toxicity”, “toxicity” and “healthy controls”. Clusters highlighted by blue boxes correspond to clusters 1, 2, 9, 12, 17 and 18 identified from Fig. 2a. These clusters are attenuated in the “toxicity” cohort in this unsupervised analysis. The box labelled “A” is encircling clusters 9 (pink) and 12 (light green). The box labelled “B” is encircling clusters 17 (deep lilac) and 18 (light lilac). The box labelled “C” is encircling clusters 1 (red) and 2 (peach). All samples are randomly downsampled to account for equally representative populations across samples. c UMAP plots stratified according to overall population IL-10 expression and by condition. Expression is largely confined to the Breg clusters demarcated by the red arrows. Matched IL-10 expression in the corresponding clusters in the toxicity patients is reduced. Although cluster 2 (peach island in (a)) is IL-10-negative in the heatmap, this is based on median marker expression and therefore does not illustrate the cell-to-cell variability in functional IL-10 status. The left-hand most red arrow depicts cluster 2 with subpopulations of IL-10 expressing cells (areas of light green and yellow), said cells are not seen in the corresponding cells in the toxicity patients.