The apoptotic signaling pathway is obviously disordered in systemic lupus erythematosus (SLE). Concurrent occurrence of induced apoptotic cell death and altered phagocytosis promotes autoantigen production, which leads to the biosynthesis of autoantibodies and autoimmune disorders. Natural IgM (nIgM) is important in clearing apoptotic cells and preventing them from triggering deleterious autoimmunity. B-1- and innate-like B- (ILBs) cells are the main nIgM producers. Human CD27+IgD+B cells (un-switched memory B cells) are considered ILBs. However, their functional properties in SLE remain undefined. Here, individuals with SLE showed markedly reduced CD27+IgD+B cell amounts. Moreover, these cells had altered function in terms of natural antibody-like IgM production. CD27+IgD+B cells also showed negative correlations with clinical and immunological properties in SLE patients. Following effective treatment achieving SLE remission, CD27+IgD+B cell amounts were restored. Jointly, these findings suggest that CD27+IgD+B cell dysfunction potentially contributes to the exacerbation of SLE, and modulating their features may represent a powerful tool for treating this persistent disease.

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.