This together with the increased numbers of CD21- naïve B-cells would contribute to a lower B-cell (activation) response (36), leading to a more pronounced anergic state, as previously associated with CD21-/low B cells in CVID (29, 30) and CD19-CD81 complex immunodeficiency (48), together with downregulation of B-cell activation receptors in parallel to upregulation of genes involved in the inhibition of B-cell proliferation (35). The gene discussed is CR2; the disease is common variable immunodeficiency.