Aberrant expression of JMJD3 in SLE promotes B-cell differentiation.

Systemic lupus erythematosus (SLE) is a typical autoimmune disease distinguished by multiple organ dysfunction, which is related to a variety of causative factors. B-cell overactivation is a key factor in SLE. However, the pathogenesis underlying anomalous B cells has not been well elucidated. B-cell fate is regulated in diverse epigenetic ways apart from traditional ways. As one of the mechanisms of epigenetics, histone modification mainly affects transcription and translation by changing the chemical groups on histones by histone modification enzymes. JMJD3, a histone demethylase, can promote T-cell proliferation in SLE patients, which exacerbates SLE. However, the mechanism of JMJD3 in B cells in SLE has not been studied. Here, we found that the mean fluorescence intensity (MFI) of JMJD3 in classical memory B cells (CMBs) was higher than that in naïve B cells (NBs) from human tonsil tissue; JMJD3 was overexpressed in B cells from the peripheral blood of SLE patients compared with healthy controls (HCs). In vitro, our experiment showed that JMJD3 could regulate B-cell differentiation by promoting naïve B-cell differentiation into CD27+ B cells, and Blimp-1 and Bcl-6 also decreased after inhibitor treatment. These findings provide a new direction for the pathogenesis of SLE and may supply a new idea for subsequent drug development.