The Study Of PD-1/PD-L1 Signaling Pathway On The Function Of B Cells In Patients With Systemic Lupus Erythematosus

Background:Systemic Lupus Erythematosus(SLE)is a chronic systemic autoimmune disease characterized by loss of tolerance to autoantigens,production of a large number of pathogenic autoantibodies,and damage to multiple organs.Autoantibodies are SLE sign features.PD-1(Programmed Cell Death-1,CD279)is a newly discovered new member of the CD28 immunoglobulin superfamily,inducibly expressed on activated T and B lymphocytes,and ligands PD-L1 and PD After L2interaction,an inhibitory signal is delivered to activated T cells.Changes in the expression of PD-1 and its ligand PD-L on the surface of B cells may play an important role in the pathogenesis of SLE.Objective:Systemic lupus erythematosus(SLE)is frequently characterized by programmed death 1(PD-1)/PD-L1 pathway activation.The present study was aimed to evaluate the function of PD-1 in SLE,and explore the mechanisms through investigating PD-1/PD-L1 pathway signaling.Methods:Flow cytometry(FCM)was assayed in B cells of SLE patients and healthy controls.Flow sorting was measured in SLE patients、healthy controls、MRL-Faslpr/Nju mice and mice controls.IgG and anti-dsDNA were measured using ELISA.Cell cycle was assayed using flow cytometry.Results:Flow cytometry studies also showed that the frequency of B cells is significantly increased in SLE patients as compared with healthy controls and that the percentage of Double negative(DN)cells and Plasmablast cells(PC)among total B cells is apparently increased in SLE patients as compared with healthy controls;Our clincal findings showed that PD-1~+B cells have a closely linked with clinical indicators;Proliferation analysis demonstrated that SLE patients PD-1~+B cells proliferative response to stimulation by CpG DNA in the absence of BCR cross-linking.Using ELISA kits,the levels of IgG increased in SLE patients and healthy controls PD-1~+B cells as compared with PD-1~-B cells which were in vitro culture for seven days;The animal experiments,After 2 weeks,Using ELISA kits,the levels of anti-dsDNA and IgG presented apparently increasedin the group of that the MRL-Faslpr/Nju mice PD-1~+B cells transferedinto MRL-Faslpr/Nju mice.Flow cytometry studies also showed that the frequency of Tfh cells is significantly increased in SLE patients as compared with healthy controls.Conclusions:Our results showed that the PD-1~+B cells were beneficial for the promoting of systemic lupus erythematosus.The increase in the proportion of TFH cells may have the ability to induce B cells to secrete antibody immunoglobulin and participate in the development of SLE.