title: T cell CD40LG gene expression and the production of IgG by autologous B cells in systemic lupus erythematosus.
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.
authors.affiliation: Department of Dermatology and Epigenetic Research Center, Second Xiangya Hospital, Central South University, 139 Renmin Middle Rd, Changsha, Hunan 410011, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.forename: Yujun
authors.initials: Y
authors.lastname: Pan
authors.forename: Yiping
authors.initials: Y
authors.lastname: Fei
authors.forename: Xiangning
authors.initials: X
authors.lastname: Qiu
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Luo
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Lei
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
authors.forename: Hai
authors.initials: H
authors.lastname: Long
authors.forename: Amr H
authors.initials: AH
authors.lastname: Sawalha
authors.forename: Bruce
authors.initials: B
authors.lastname: Richardson
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000235:genetics* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D012727:Sex Characteristics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D023201:CD40 Ligand