title: Reduced BAFF-R and increased TACI expression in common variable immunodeficiency.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal.
authors.forename: Rita R
authors.initials: RR
authors.lastname: Barbosa
authors.forename: Susana L
authors.initials: SL
authors.lastname: Silva
authors.forename: Sara P
authors.initials: SP
authors.lastname: Silva
authors.forename: Alcinda C
authors.initials: AC
authors.lastname: Melo
authors.forename: M Conceição
authors.initials: MC
authors.lastname: Pereira-Santos
authors.forename: João T
authors.initials: JT
authors.lastname: Barata
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
authors.forename: Marília
authors.initials: M
authors.lastname: Cascalho
authors.forename: Ana E
authors.initials: AE
authors.lastname: Sousa
mesh_terms: D053264:B-Cell Activating Factor / Q000235:genetics* / Q000276:immunology; D053265:B-Cell Activation Factor Receptor / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013163:Splenomegaly / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics* / Q000276:immunology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000276:immunology
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D012333:RNA, Messenger; D011994:Recombinant Proteins; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13