B-cell–to–T-cell cross talk model at single-cell level. (A) Schematic representation of the expected B-cell–to–T-cell crosstalk model. In the top panel the normal B/T condition is shown; the bottom panel depicts the model of the proposed B-cell–to–T-cell interaction, with clonal B cells releasing factor(s) responsible for the induction of CD4⁺ T-cell differentiation to Tregs. (B) Heatmap representing the top candidate protein-protein interactions occurring between B (ligands, y-axis) and T (receptors, x-axis) cells in WMCL1 and WMCL1-CXCR4^C1013G cells. CD40/CD40LG interactors are shown in bold. (C) Violin plots showing the normalized expression level of all the candidate receptors expressed by B cells (B) in CD19, WMCL1, and WMCL1-CXCR4^C1013G cells. (D) tSNE plots highlighting the expression level of top B-cell (top) and T-cell (bottom) interactors. B-cell markers are represented in an orange (high expression) to blue (low expression) color scale; Treg markers are represented in a yellow (high expression) to blue (low expression) color scale. (E) Percentage of Tregs after exposure to normal CD19, BCMW.1, or BCWM.1-CXCR4^C1013G cells. (F) Heatmap representing the top candidate protein-protein interactions occurring between B (ligands, y-axis) and T (receptors, x-axis) cells in BCMW.1 and BCWM.1-CXCR4^C1013G cells. CD40/CD40LG interactors are shown in bold. (G) Violin plots showing the normalized expression level of CD40 in normal CD19, BCWM.1, or BCWM.1-CXCR4^C1013G cells.