title: B cell co-receptors regulating T cell-dependent antibody production in common variable immunodeficiency: CD27 pathway defects identify subsets of severely immuno-compromised patients.
abstract: CD27 and CD134 ligand (CD134L) are two B cell co-receptors for T(h) cell activation-induced ligands (i.e. CD70 and CD134) that promote differentiation of B cells into plasma cells and high-rate antibody production respectively. We explored the CD27 pathway and T cell CD134 expression in common variable immunodeficiency (CVID), a disease characterized by a lack of plasma cells and low Ig serum levels. Twelve patients were compared to seven healthy controls. We found a low percentage of circulating CD27(+) B cells in seven patients and B cell CD27 expression was not up-regulated by in vitro activation in two of them. Importantly, the number of circulating CD27(+) B cells was correlated with the severity of the disease--the patients with the lowest CD27(+) B cell counts having the lowest serum Ig concentrations and the lowest total peripheral blood B cell counts. In contrast, CD70 and CD134 were normally expressed on in vitro activated T cells. CD134L was not detected on patient and control B cells in our activation conditions. Functional studies of in vitro Ig production demonstrated an absence of B cell response to CD27 cross-linking, in particular in a patient with normal CD27 expression. Our results indicate that a defect in CD27 expression or function contributes to the pathogenesis of certain severe forms of CVID.
authors: INSERM U519, IFRMP 23, Laboratoire d'Immunopathologie Clinique et Expérimentale, CHU Charles Nicolle, Faculté de Médecine et de Pharmacie, 22 boulevard Gambetta, 76183 Rouen Cedex, France.
authors: S
authors: S
authors: Jacquot
authors: L
authors: L
authors: Maçon-Lemaître
authors: E
authors: E
authors: Paris
authors: T
authors: T
authors: Kobata
authors: Y
authors: Y
authors: Tanaka
authors: C
authors: C
authors: Morimoto
authors: S F
authors: SF
authors: Schlossman
authors: F
authors: F
authors: Tron
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D053282:CD27 Ligand; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D003432:Cross-Linking Reagents; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D013601:T-Lymphocytes / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; D003432:Cross-Linking Reagents; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7