OBJECTIVE To investigate the contribution of B cell activating factor of TNF family(BAFF)in the proliferation and activation of B cell in rheumatoid arthritis(RA),and to clarify whether high levels of BAFF is associated with clinical variables and lab parameters.METHODS Blood samples and peripheral blood mononuclear cells from RA patients and healthy controls(HCs)were collected and isolated respectively.Clinical variables and lab parameters,BAFF level,cytokines and immunoglobulins in serum were evaluated at entry.B cell subpopulations,BAFF receptors(BAFFR,BCMA,TACI),and alternative and canonical NF-κB pathway in B cell were analyzed in vivo and in vitro.RESULTS In RA patients,BAFF level and activated B cell subsets increased significantly.BAFF level was associated with CRP,RF,DAS28,swollen joint counts and tender joint counts.BAFFR,BCMA,TACI on B cells in RA over expressed.The expressions of MKK3,MKK6,p-p38,p-NF-κB65,TRAF2,NF-κB52 were higher than that in HCs.In vitro,BAFF up regulated activated B cell subset and the expressions of BAFFR,BCMA and TACI.BAFF also enhanced the expressions of MKK3,MKK6,p-p38,p-NF-κB65,TRAF2,NF-κB52.CONCLUSION Increased BAFF in serum is associated with the disease activity of RA,BAFF involves in the proliferation and activation of B cell in RA through alternative and canonical NF-κB pathway,indicating that BAFF might be a novel biomarker of diagnosis and therapy.