CD 27 + B cells from a subgroup of common variable immunodeficiency patients are less sensitive to apoptosis rescue regardless of interleukin‐21 signalling

Summary Common variable immunodeficiency ( CVID ) is a primary immunodeficiency characterized by hypogammaglobulinaemia and recurrent infections. Although the underlying cause is unknown, B cells from most CVID patients fail to differentiate to memory or plasma cells. We investigated if increased apoptosis could influence the fate of B cells. For this purpose we activated purified B lymphocytes of CVID patients with a surrogate T ‐dependent (anti‐ CD 40) or T ‐independent [cytosine–phosphate–guanosine oligodeoxynucleotides ( CpG‐ODN ) or anti‐immunoglobulin ( Ig)M )] stimulus with or without interleukin ( IL )‐21. We found that CD 27 + B cells were more sensitive than CD 27 – B cells to spontaneous apoptosis and less sensitive to rescue from apoptosis. The addition of IL ‐21 down‐modulated the protective effect of all the stimuli on CD 27 – B cells and the protective effect of CpG ‐ ODN and anti‐ IgM on CD 27 + B cells. In contrast, IL ‐21 rescued unstimulated CD 27 – B cells and improved the rescue of anti‐ CD 40‐stimulated CD 27 + B cells. When we compared patients and controls, mainly CD 27 + B cells from MB0 patients were less sensitive to rescue from apoptosis than those from MB 1 patients and controls after activation, irrespective of the IL ‐21 effect. Increased apoptosis during an immune response could result in lower levels of immunoglobulin production in these patients.