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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.

international immunology

B cell co-receptors regulating T cell-dependent antibody production in common variable immunodeficiency: CD27 pathway defects identify subsets of severely immuno-compromised patients