Mutational Analysis of Human BAFF Receptor TNFRSF13C (BAFF-R) in Patients with Common Variable Immunodeficiency
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BAFF receptor (BAFF-R/BR3/TNFRSF13C) is a recently identified molecule that specifically binds BLyS, a protein belonging to the tumor necrosis factor (TNF) family, and is involved in survival and maturation of B cells. Recent studies have demonstrated that mice defective in BAFF-R gene exhibit an altered profile of the B cell pool, a phenotype observed in BLyS knockout mice as well. These features suggest that mutations in this gene may result in humoral immunodeficiency. To test this hypothesis, we sequenced the BAFF-R gene in 48 patients with common variable immunodeficiency (CVID) along with 57 healthy controls. We have identified three novel variants present at the heterozygous state leading to amino acid substitutions, and have also confirmed the existence of a previously reported intronic variant. The hereby described novel variants were also present in healthy controls and in the healthy patients’ parents. These variants do not affect the expression of BAFF-R neither at the mRNA nor at the protein level, suggesting that these variants represent novel polymorphic variants of the BAFF-R gene.
KeywordsCVID B cell differentiation genomic polymorphic variants mRNA expression
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- 2.Grimbacher B, Hutloff A, Schlesier M, Glocker E, Warnatz K, Dräger R, Eibel H, Fischer B, Schäffer A, Mages HW, Kroczek RA, Peter HH: Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol 4:261–268, 2003Google Scholar
- 3.Gross JA, Dillon SR, Mudri S, Johnston J, Littau A, Roque R, Rixon M, Schou O, Foley KP, Haugen H, McMillens S, Waggie K, Schrechhise RV, Shoemaker K, Vu T, Moore M, Grossman A, Clegg CH: TACI-Ig neutralized molecules critical for B cell development and autoimmune disease. Impaired B cell maturation in mice lacking BLyS. Immunity 15:289–302, 2001CrossRefPubMedGoogle Scholar
- 4.Schiemann B, Gommerman JL, Vora K, Cachero TG, Shulga-Morskaya S, Dobles D, Frew E, and Scott ML: An essential role for BAFF in the normal development of B cells trough a BCMA-independent pathway. Science 293:2111–2114, 2001Google Scholar
- 6.Bodmer JL, Shneider P, Tschopp J: The molecular architecture of the TNF superfamily. TIBS 27:18–26, 2002Google Scholar
- 7.Thompson JS, Bixler SA, Quian F, Vora K, Scott ML, Cachero TG, Heisson C, Schneider P, Sizing ID, Mullen C, Strauch K, Zafari M, Benjamin CD, Tschopp J, Browning JL, Ambrose C: BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF. Science 293:2108–2111, 2001CrossRefPubMedGoogle Scholar
- 12.Ng LG, Sutherland AP, Newton R, Qian F, Cachero TG, Scott ML, Thompson JS, Wheway J, Chtanova T, Groom J, Sutton IJ, Xin C, Tangye SG, Kalled SL, Mackay F, Mackay CR: B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells. J Immunol 173:807–817, 2004PubMedGoogle Scholar