The properties of antibody-secreting cells (ASCs) and the contribution of these cells to serum autoantibodies during flares of systemic lupus erythematosus (SLE) activity are unknown. New findings by Tipton et al. show that circulating ASCs that are present during SLE flares are highly polyclonal but contain clonal expansions that express the variable heavy-chain region VH4–34. The researchers also found that a substantial proportion of ASCs were derived from newly activated naive B cells, providing insight into the mechanisms of B cell hyperactivity in SLE.