Dissecting The Roles Of B Cells In The Pathogenesis Of Systemic Lupus Erythematosus

Objective:Systemic lupus erythematosus(SLE)is a prototypic autoimmune disease,characterized with high titers of circulating autoantibody.Our lab had identified a novel T-bet+CD11c+B cell subset which was responsible for the production of anti-chromatin antibody in lupus-like chronic graft-versus-host disease(cGVHD).Pbx1 is a susceptible gene of lupus,which plays an important role in regulating tissue and organ development,tumorigenesis and cell differentiation.Therefore,the purpose of this study was to explore the correlation between T-bet+CD11c+B cells and autoantibodies in SLE patients,and the role of Pbx1 on B cell function during the development of SLE.Methods:Induction of lupus-like cGVHD model and experimental allergic cerebrospinal meningitis(EAE)model.Flow cytometry was used to analyze human samples and mice splenocytes.Magnetic beads were used to isolate cell subset.RT-q PCR was used to detect the expression of genes.ELISA was used to detect antibodies in serum and supernatants.Results:Depletion of CD11c+B cells reduced anti-chromatin Ig G and Ig G2a production.The percentage of T-bet~+CD11c~+B cells was elevated in lupus patients and correlated with serum anti-chromatin levels and disease activity.The expression of Pbx1 was significantly reduced in B cells from lupus patients and mice,and was inhibited with TLRs stimulation.Deletion Pbx1 in B cells promoted inflammatory cytokines production in mice.B cell specific Pbx1 depletion aggravated EAE and increases pathogenic CD4~+T cells in the CNS.Furthermore,we found that deletion Pbx1 in B cell have no significant effect on the development of B cell or the production of T cell dependent antibody.Conclusion:The percentage of T-bet+CD11c+B cells are associated with anti-chromatin antibodies in SLE patients.Pbx1 expression in B cells from SLE patients and mouse was decreased,and depletion of Pbx1 in B cells can promote the abnormal secretion of inflammatory factors,aggravated EAE.