TACI mutations and impaired B-cell function in subjects with CVID and healthy heterozygotes

Monica Martinez-Gallo, Lin Radigan, María Belén Almejún, Natalia Martínez-Pomar, Núria Matamoros, Charlotte Cunningham-Rundles*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

73 Citations (Scopus)


Background: Mutations in the gene coding for the transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) are found in 8% to 10% of subjects with common variable immunodeficiency (CVID). Although heterozygous mutations may coincide with immunodeficiency in a few families, most mutation-bearing relatives are not hypogammaglobulinemic. Thus, the role of TACI mutations in producing the immune defect remains unclear. Objective: This study examined the expression and function of TACI mutations in healthy heterozygous relatives. Methods: We examined the surface and intracellular expression of TACI protein in EBV-transformed B cells of patients and relatives with mutations in 7 families, binding of a proliferation-inducing ligand, and secretion of IgG and IgA by ligand-activated B cells. We tested whether Toll-like receptor 9 agonists increased TACI expression and whether an agonistic anti-TACI antibody could induce activation-induced cytidine deaminase mRNA in those with mutations. Results: Intracellular and extracellular TACI expression was defective for B cells of all subjects with mutations, including subjects with CVID and relatives. Although Toll-like receptor 9 triggering normally up-regulates B-cell TACI expression, this was defective for all subjects with mutations. Triggering TACI by an agonistic antibody showed loss of activation-induced cytidine deaminase mRNA induction in all mutation-bearing B cells. However, ligand-induced IgG and IgA production was normal for healthy relatives but not for subjects with CVID. Conclusion: Thus, B cells of relatives of subjects with CVID who have mutations in TACI but normal immune globulin levels still have detectable in vitro B-cell defects.

Original languageEnglish
Pages (from-to)468-476
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Issue number2
Publication statusPublished - Feb 2013


  • activation-induced cytidine deaminase
  • CVID
  • hypogammaglobulinemia
  • TACI
  • Toll-like receptor 9


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