Fig. 10: METTL1 promotes B-cell responses in systemic autoimmunity.

a–c scRNA-seq data analysis of B-cell subclusters from systemic lupus erythematosus (SLE) patients and HCs. a UMAP displaying B-cell clustering. b Dot plot displaying Mettl1 and Wdr4 expression in SLE patients and HCs. c Dot plot displaying Mettl1 and Wdr4 expression in B-cell clusters. d Gating strategy for B-cell subsets in PBMCs. e, f Representative flow cytometry plots and MFIs of METTL1 expression among SLE B-cell subsets gated on d (n = 12 biological independent samples). g MFIs of METTL1 expression in PBMC B cells (SLE = 12 biological independent samples, HCs = 10 biological independent samples). h Correlation between MFI of METTL1 expression in PBMC B cells and disease activity (SLEDAI) in SLE patients (simple linear regression analysis was used). i METTL1 and WDR4 expression in B cells from HCs and SLE patients was measured by western blotting. Representative bands were shown. j m⁷G levels in B cells from HCs and SLE patients were quantified by northern blotting. Representative bands were shown. k–r SLE B cells were transfected with shMettl1 or vector. k The phosphorylation of PI3K and AKT in HC B cells, SLE B cells, and SLE B cells treated with shMettl1 was measured by western blotting. Representative bands were shown. l Heatmap displaying the results of qPCR analysis of the ETC genes in HC B cells, SLE B cells, and SLE B cells treated with shMettl1 (n = 3 biological independent samples). m SDHB and NDUFA12 expression in HC B cells, SLE B cells, and SLE B cells treated with shMettl1 were measured by western blotting. Representative bands were shown. n, o Seahorse assay measuring mitochondrial respiration in HC B cells, SLE B cells, and SLE B cells treated with shMettl1 (n = 4 biological independent samples). The OCRs are displayed in n and summarized in o. p Representative flow cytometry plots of CD27^hiCD38^hi ASCs in HCs and SLE patients. q, r Representative flow cytometry plots and frequencies of ASC differentiation from SLE B cells (n = 8 biological independent samples). The data are presented as the mean ± SEM. A two-tailed unpaired Student’s t test in g and a two-tailed paired Student’s t test in r, paired one-way ANOVA in f, and one-way ANOVA in o. Source data are provided as a Source Data file.