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

CD27 and CD134 ligand (CD134L) are two B cell co-receptors for T-h cell act ivation-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 variab le immunodeficiency (CVID), a disease characterized by a lack of plasma cel ls 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 upregulated by in vitro activa tion in two of them. Importantly, the number of circulating CD27(+) B cells was correlated with the severity of the disease-the patients with the lowe st CD27(+) B cell counts having the lowest serum Ig concentrations and the lowest total peripheral blood 13 cell counts. In contrast, CD70 and CD134 w ere normally expressed on in vitro activated T cells. CD134L was not detect ed on patient and control IS cells in our activation conditions. Functional studies of in vitro Ig production demonstrated an absence of B cell respon se to CD27 cross-linking, in particular in a patient with normal CD27 expre ssion. Our results indicate that a defect in CD27 expression or function co ntributes to the pathogenesis of certain severe forms of CVID.