Reduced BAFF-R and Increased TACI Expression in Common Variable Immunodeficiency
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B-cell survival and differentiation critically depend on the interaction of BAFF-R and TACI with their ligands, BAFF and APRIL. Mature B-cell defects lead to Common Variable Immunodeficiency (CVID), which is associated with elevated serum levels of BAFF and APRIL. Nevertheless, BAFF-R and TACI expression in CVID and their relationship with ligand availability remain poorly understood.
Methods and Results
We found that BAFF-R expression was dramatically reduced on B cells of CVID patients, relative to controls. BAFF-R levels inversely correlated with serum BAFF concentration both in CVID and healthy subjects. We also found that recombinant BAFF stimulation reduced BAFF-R expression on B cells without decreasing transcript levels. On the other hand, CVID subjects had increased TACI expression on B cells in direct association with serum BAFF but not APRIL levels. Moreover, splenomegaly was associated with higher TACI expression, suggesting that perturbations of TACI function may underlie lymphoproliferation in CVID.
Our results indicate that availability of BAFF determines BAFF-R and TACI expression on B cells, and that BAFF-R expression is controlled by BAFF binding. Identification of the factors governing BAFF-R and TACI is crucial to understanding CVID pathogenesis, and B-cell biology in general, as well as to explore their potential as therapeutic targets.
KeywordsB cells BAFF-R TACI BAFF common variable immunodeficiency
We would like to thank Elisa Pedro and Manuel Barbosa from the Department of Immunoallergology of the University Hospital de Santa Maria, Lisbon, Portugal, for the clinical collaboration; Rui M. M. Victorino, Íris Caramalho, Adriana S. Albuquerque and Russell B. Foxall for the helpful discussions and critical revision of the manuscript, as well as Ana Isabel Pinheiro, Ana Rita Pires and Paula Matoso, for the invaluable technical assistance, all from the Instituto de Medicina Molecular, Lisbon, Portugal. R.R.B. and S.L.S. received PhD scholarships from Fundação para a Ciência e Tecnologia (FCT) and Programa Operacional Ciência e Inovação 2010, Portugal.
Conflict of Interest Disclosures
The authors declare that they have no conflict of interest.
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