Apoptotic signaling pathway is obviously disordered in systemic lupus erythematosus (SLE). The contemporaneous occurrence of enhanced apoptosis and impaired phagocytosis lead to the cumulative exposure to autoantigens, resulting in autoantibody production and autoimmunity. Natural IgM (nIgM) plays a key role in the clearance of apoptotic cells and prevents them from inducing abnormal autoimmunity. B-1 cells and innate-like B cells (ILBs) are proved to be the major producer of natural IgM. Human CD27+IgD+B cells, also termed as un-switched memory B cells, are recently proposed to be a kind of ILBs. However, functional features and characteristics of these cells in SLE remain poorly understood.In this study, we find that in SLE patients the frequencies of CD27+IgD+B cells are significantly decreased. Moreover, these cells are functionally impaired in producing natural antibody-like IgM. These CD27+IgD+B cells are negatively correlated with SLE patient clinical and immunological features. After effective therapy with disease remission in SLE, the frequencies of these cells could be recovered. Taken together, our results suggest that the dysfunction of CD27+IgD+B cells potentially contribute to the exacerbation of SLE, and modulating the features of these cells might provide therapeutic target for this persistent disease.