title: CD27+ B cells from a subgroup of common variable immunodeficiency patients are less sensitive to apoptosis rescue regardless of interleukin-21 signalling.
abstract: 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-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.
authors.affiliation: Department of Immunology, Hospital Universitari Son Espases, Palma de Mallorca, Spain; Fundació d'Investigació Sanitària de les Illes Balears (FISIB), Palma de Mallorca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Clemente
authors.forename: J
authors.initials: J
authors.lastname: Pons
authors.forename: N
authors.initials: N
authors.lastname: Lanio
authors.forename: N
authors.initials: N
authors.lastname: Matamoros
authors.forename: J M
authors.initials: JM
authors.lastname: Ferrer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007378:Interleukins / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000098546:Interleukin-21
keywords: CD27+ B cells; CVID; IL-21; TRAIL; apoptosis