Abstract
CD40 ligand (CD40LG), encoded on the X chromosome, has been reported to be overexpressed on lupus T cells. Herein, we investigated the effect of DNA demethylation on T cell CD40LG expression and the production of IgG by autologous B cells in lupus. We found normal human T cells transfected with CD40LG induced autologous B cell activation and plasma cell differentiation. Both female lupus CD4+ T cells and demethylating agents treated CD4+ T cells overexpressed CD40LG mRNA. Further, lupus T cells from both genders or demethylated CD4+ T cells from healthy women overstimulated autologous B cells, and this could be reversed with anti-CD40LG Ab in only females. We demonstrated that female lupus CD4+ T cells and demethylated CD4+ T cells express high level of CD40LG and overstimulate B cells to produce IgG. This is due to DNA demethylation and thereby reactivation of the inactive X chromosome in female.