CD21 and CD23, which in mouse and human spleen are fundamental for the adjudication of follicular and marginal zone phenotypes (13, 24, 84), are expressed universally by unperturbed human blood naïve B cells and their downregulation is observed in a major fraction of naïve B cells in several immunological conditions, including SLE (41, 85). Here, CR2 is linked to systemic lupus erythematosus.