CD27+ B cells from a subgroup of common variable immunodeficiency patients are less sensitive to apoptosis rescue regardless of interleukin-21 signalling


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Abstract

SummaryCommon 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-CD40) or T-independent [cytosine–phosphate–guanosine oligodeoxynucleotides (CpG-ODN) or anti-immunoglobulin (Ig)M)] stimulus with or without interleukin (IL)-21. We found that CD27+ B cells were more sensitive than CD27 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 CD27 B cells and the protective effect of CpG-ODN and anti-IgM on CD27+ B cells. In contrast, IL-21 rescued unstimulated CD27 B cells and improved the rescue of anti-CD40-stimulated CD27+ B cells. When we compared patients and controls, mainly CD27+ B cells from MB0 patients were less sensitive to rescue from apoptosis than those from MB1 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.

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