Bach2 in CD4+ T cells from SLE patients modulates B-cell differentiation and IgG production

T and B cells participate in the development of systemic lupus erythematosus (SLE). BTB and CNC homology 2 (Bach2) is an irreplaceable regulator in the T and B lineages that helps to maintain immune homeostasis. However, the function of Bach2 in the pathogenesis of SLE has not been studied in depth. Flow cytometry and qRT-PCR were used to assess Bach2 levels, bisulfite sequencing PCR was used to measure the methylation level, and silencing by electroporation and stimulation with a cytokine concentration gradient were used to investigate the effect of Bach2 on T cells. Bach2 expression was elevated in the helper T-cell subsets (T follicular helper, Th1, Th2, Th17, and Treg cells) of SLE patients and negatively correlated with disease severity and autoantibody levels. CD4(+) T cells from SLE patients had decreased methylation levels in the Bach2 promoter region. Silencing Bach2 in CD4(+) T cells induced increases in the CD19(+) B-cell count, plasmablasts, and secretion of IgG by prompting the secretion of cytokines. The activation signals CD3/CD28, IL-6, and IL-21 upregulated Bach2 expression in CD4(+) T cells. The regulation of Bach2 by cytokines and T-cell activation signals in CD4(+) T cells was shown to act on B cells and play a protective role against SLE.

Automated summary

Bach2 plays an important regulatory role in T and B cells, and it is also involved in the pathogenesis of systemic lupus erythematosus (SLE). The expression of Bach2 in helper T-cell subsets is elevated in SLE patients and negatively correlated with disease severity and autoantibody levels. Silencing Bach2 in CD4(+) T cells promotes the increase of CD19(+) B-cell count, plasmablasts, and secretion of IgG.