Fig. 5: METTL1 controls the GC B-cell responses via BCR signaling. | Nature Communications

Fig. 5: METTL1 controls the GC B-cell responses via BCR signaling.

From: Aberrant METTL1-mediated tRNA m7G modification alters B-cell responses in systemic autoimmunity in humans and mice

Fig. 5

a Volcano plot displaying DEGs between cKO B cells and WT control B cells through RNA-seq (p value via “limma” R package). b Top 10 terms enriched with downregulated mRNA in Mettl1-deleted B cells (adjusted p value via “clusterProfiler” GO-BP analysis). c Top 10 terms enriched with downregulated proteins in Mettl1-deleted B cells via Reactome pathway analysis (adjusted p value via “clusterProfiler” Reactome analysis). d–g Ribo-seq analysis of WT and cKO spleen B cells. d Scatterplots displaying the translation efficiency (TE) of genes in B cells from WT and cKO mice. e Frequency of m7G tRNA-decoded codon usage in genes with increased TEs (TE-up) and decreased TEs (TE-down) in Mettl1-deleted B cells (n = 1 mouse for each group). The upper whisker is 75th percentile plus 1.5*IQR, and the lower whisker is 25th percentile minus 1.5*IQR. The upper and lower bounds of box are 75th and 25th percentile, respectively, the center is median, and points show outliers. f Codon frequency of m7G tRNA-decoded codons in TE-down genes. g GO terms enriched with downregulated TE genes in Mettl1-deleted B cells (p value via “clusterProfiler” R package). h Volcano plot displaying nonsignificant changes in Cd19 expression via RNA-seq and significant downregulation of CD19 in Mettl1-deleted B cells via proteomic data (p value via “limma” R package). i, j Representative flow plot and summarized data showing CD19 expression levels in WT or Mettl1-deleted B cells (n = 4). k Bar plots displaying the relative TE changes after the transfection of WT-Cd19 or MUT-Cd19 with base mutations in specific codon plasmids into Mettl1-knockdown 293 T cells and control 293 T cells (n = 3). l Representative flow plot and summary data showing surface IgM (sIgM) expression levels in WT or Mettl1-deleted B cells (WT = 5 and cKO = 4). m The expression of p-SYK, p-BTK, p-PI3K, and p-AKT in WT or Mettl1-deleted B cells was measured via western blot and representative bands. n, o GC B cells or PCs were induced in vitro (n = 4). Representative plots are shown. Biological independent samples for j–l, o. The data are presented as the mean ± SEM. A two-tailed Mann–Whitney test was used in e, and a two-tailed unpaired Student’s t-test was used in j–l, o. Source data are provided as a Source Data file.

Back to article page