title: B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans.
abstract: B-cell survival depends on signals induced by B-cell activating factor (BAFF) binding to its receptor (BAFF-R). In mice, mutations in BAFF or BAFF-R cause B-cell lymphopenia and antibody deficiency. Analyzing BAFF-R expression and BAFF-binding to B cells in common variable immunodeficiency (CVID) patients, we identified two siblings carrying a homozygous deletion in the BAFF-R gene. Removing most of the BAFF-R transmembrane part, the deletion precludes BAFF-R expression. Without BAFF-R, B-cell development is arrested at the stage of transitional B cells and the numbers of all subsequent B-cell stages are severely reduced. Both siblings have lower IgG and IgM serum levels but, unlike most CVID patients, normal IgA concentrations. They also did not mount a T-independent immune response against pneumococcal cell wall polysaccharides but only one BAFF-R-deficient sibling developed recurrent infections. Therefore, deletion of the BAFF-R gene in humans causes a characteristic immunological phenotype but it does not necessarily lead to a clinically manifest immunodeficiency.
authors: Department of Rheumatology and Clinical Immunology and Center for Chronic Immunodeficiencies, University Medical Center Freiburg, 79106 Freiburg, Germany.
authors: Klaus
authors: K
authors: Warnatz
authors: Ulrich
authors: U
authors: Salzer
authors: Marta
authors: M
authors: Rizzi
authors: Beate
authors: B
authors: Fischer
authors: Sylvia
authors: S
authors: Gutenberger
authors: Joachim
authors: J
authors: Böhm
authors: Anne-Kathrin
authors: AK
authors: Kienzler
authors: Qiang
authors: Q
authors: Pan-Hammarström
authors: Lennart
authors: L
authors: Hammarström
authors: Mirzokhid
authors: M
authors: Rakhmanov
authors: Michael
authors: M
authors: Schlesier
authors: Bodo
authors: B
authors: Grimbacher
authors: Hans-Hartmut
authors: HH
authors: Peter
authors: Hermann
authors: H
authors: Eibel
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D053265:B-Cell Activation Factor Receptor / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D001402:B-Lymphocytes / Q000378:metabolism; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D006720:Homozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data
chemical_list: D053265:B-Cell Activation Factor Receptor; C435926:TNFRSF13C protein, human