Xist Deletion in B Cells Results in Systemic Lupus Erythematosus Phenotypes

X-linked gene expression in XX females is normalized to that of XY males by XChromosome Inactivation (XCI). However, B cells from female SLE patients and mouse models of SLE exhibit mislocalization of Xist RNA, a critical regulator of XCI, and aberrant expression of X-linked genes, suggesting that impairment of XCI may contribute to disease.

Here, we find that a subset of female mice harboring a conditional deletion of Xist in B cells (“Xist cKO”) spontaneously develop SLE phenotypes, including expanded activated B cell subsets, diseasespecific autoantibodies, and glomerulonephritis. Moreover, pristane-induced SLE-like disease is more severe in Xist cKO mice. Activated B cells from Xist cKO mice with SLE phenotypes have increased expression of proinflammatory X-linked genes implicated in SLE.