T cell CD40LG gene expression and the production of IgG by autologous B cells in systemic lupus erythematosus.
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.
Zhou
Ying
Y
Department of Dermatology and Epigenetic Research Center, Second Xiangya Hospital, Central South University, 139 Renmin Middle Rd, Changsha, Hunan 410011, PR China.
Yuan
Jun
J
Pan
Yujun
Y
Fei
Yiping
Y
Qiu
Xiangning
X
Hu
Nan
N
Luo
Yongqi
Y
Lei
Wenzhi
W
Li
Yaping
Y
Long
Hai
H
Sawalha
Amr H
AH
Richardson
Bruce
B
Lu
Qianjin
Q
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
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D023201:CD40 Ligand