Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus: Delineation by expression of CD27, IgD, and CD95

Abstract Objective Analysis of peripheral B cell subsets in patients with systemic lupus erythematosus (SLE) has provided evidence of specific alterations, such as an expansion of CD27++ plasma cells/blasts and transitional B cells. However, memory B cells in lupus have not been thoroughly investigated, and only recently a CD27− memory B cell subset was identified in the peripheral blood of lupus patients. Focusing on CD27− B cells, this study aimed to identify abnormalities in peripheral B cell subsets in patients with SLE. Methods Three independent cohorts of lupus patients were used to characterize CD27− memory B cells, using multiparameter flow cytometry and single‐cell reverse transcription–polymerase chain reaction of heavy‐chain transcripts. Results We identified a homogeneous subset of CD27−,IgD−,CD95+ memory B cells with an activated phenotype that was increased in patients with disease flares and that correlated with disease activity and serologic abnormalities. In contrast, the entire subset of CD27−,IgD− B cells was found to be heterogeneous, did not correlate significantly with lupus activity, and was also increased in patients with bacterial infections. Conclusion We conclude that CD95 is a useful marker to identify CD27− memory B cells with an activated phenotype, which might serve as a biomarker for lupus activity and as a target of further investigations aiming to elucidate the pathogenic potential of these cells and the mechanisms involved in the generation as well as regulation of this CD27−,IgD−,CD95+ memory B cell subset.