Fig. 4: CREBBP and KMT2D haploinsufficiency cooperatively skews the GC B cell fate toward CB over exit differentiation into MB and PC.

a–e Single-cell RNA-seq profiling of splenic B220⁺IgD⁻ cells sorted from SRBC-immunized mice (8-weeks, female, C57BL/6J background) at day 10. a UMAP plot showing identified cell types, with GC B cell subtypes color highlighted. b Seurat dot plot showing the average expression and percent of cells expressing the indicated gene signatures in different GC B subtypes. c Bar plot depicting the proportion of different GC B subtypes in each genotype. d Cell density plot showing the distribution of different GC B subtypes along a Slingshot pseudotime axis anchored at CB. e Top, gene signature module scores were plotted for each cell along the pseudotime axis, with a best fit spline curve representing the average score. Gray bands represent 95% confidence intervals. Bottom, differential expression was shown as a delta spline plot across pseudotime and colored based on statistical significance for each bin. f, g FACS analysis showing the relative abundance of MB (f, n = 5 mice per genotype) or PC (g, left to right: n = 5/5/4/5 mice) vs GC B cells at day 10 post-SRBC (mean ± SD). h Experimental scheme for CD40L blocking assay (results shown in i, j n = 5 mice per group). i FACS data showing the ratio of WT, C, K or CK-derived GC B cell percentage to their respective parental total B cell percentage in either control IgG or CD40L blocking antibody treated mice. Each pair of connected dots represents a mouse, two-tailed paired Student’s t test. j GCB (CD45%) / B cell (CD45%) ratio fold change (i.e., C/WT, K/WT, and CK/WT) in either control IgG or CD40L blocking antibody treated mice, mean ± SD, two-tailed unpaired Student’s t test. k Graphical representation depicting the cell state transitions within GC. Upward and downward black arrows indicate cell abundance increase and decrease respectively in CK vs WT. P values were determined using two-tailed Fisher’s exact test (c), two-tailed Wilcoxon rank sum test (d, e), ordinary one-way ANOVA followed by Tukey–Kramer’s post-test (f, g). Source data are provided as a Source Data file.