Fig. 8: The Mef2bP297L lymphoma-associated mutant enhances GC formation in mice. | Nature Communications

Fig. 8: The Mef2bP297L lymphoma-associated mutant enhances GC formation in mice.

From: MEF2B C-terminal mutations enhance transcriptional activity and stability to drive B cell lymphomagenesis

Fig. 8

a Amino acid sequence alignment of human MEF2B S324 phosphorylation region with the orthologous mouse Mef2b sequence. Human P325 and the conserved murine P297 aa are displayed in bold. b Percentage of splenic GC B cells (B220+/GL7hi/CD95hi) in Mef2b+/+;Cγ1-Cretg/+ (WT), Mef2bP297L/+;Cγ1-Cretg/+ (HET) and Mef2bP297L/P297L;Cγ1-Cretg/+ (HOMO) mice, as measured by flow cytometry 10 days post-SRBC immunization. c Top, immunohistochemistry for the GC marker PNA on representative spleen sections. Scale bars, 500 μm. Bottom, average GC size and numbers, as measured by quantification of PNA staining on spleen tissue sections in a subset of the mice displayed in (b). d Ratios between dark zone (DZ: CXCR4hi/CD86lo) and light zone (LZ: CXCR4lo/CD86hi) GC B cells (B220+/GL7hi/CD95hi) from WT, HET and HOMO mice. e DZ and f LZ B cell numbers normalized by spleen weight in a subset of the mice displayed in (d). g Gene set enrichment analysis (GSEA) in WT versus HOMO GC B cell RNA-seq data using previously reported mouse and human DZ versus LZ gene signatures41. NES, normalized enrichment score. h CD86 mean fluorescence intensity (MFI) in GC B cells (B220+/GL7hi/CD95hi) measured by flow cytometry analysis and displayed as fold change relative to WT mice. i GSEA in WT versus HOMO GC B cell RNA-seq data using the top 300 genes displaying co-binding of MEF2B and SMARCA4 in their regulatory regions as identified by Cut&Run-seq analysis in human GC B cells isolated from tonsil tissue. The enrichment is measured by ranking all the assessed transcripts in the RNA-seq profiles and evaluating any distribution bias along the ranked gene list. NES, normalized enrichment score. Dot plots display average ± SD for the number of animals reported in parentheses. The p values in dot plots were determined by one-way ANOVA with Dunnett’s Multiple Comparison Test. Source data are provided as a Source Data file.

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