B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans.
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.
Warnatz
Klaus
K
Department of Rheumatology and Clinical Immunology and Center for Chronic Immunodeficiencies, University Medical Center Freiburg, 79106 Freiburg, Germany.
Salzer
Ulrich
U
Rizzi
Marta
M
Fischer
Beate
B
Gutenberger
Sylvia
S
Böhm
Joachim
J
Kienzler
Anne-Kathrin
AK
Pan-Hammarström
Qiang
Q
Hammarström
Lennart
L
Rakhmanov
Mirzokhid
M
Schlesier
Michael
M
Grimbacher
Bodo
B
Peter
Hans-Hartmut
HH
Eibel
Hermann
H
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
D053265:B-Cell Activation Factor Receptor; C435926:TNFRSF13C protein, human