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.

Ingår i:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences106:33, s. 13945-139501091-6490
Ingår i:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences106:33, s. 13945-139500027-8424

Av författaren/redakt...: Warnatz, K; Salzer, U; Rizzi, M; Fischer, B; Gutenberger, S; Bohm, J; visa fler...; Kienzler, AK; Pan-Hammarstrom, ...; Hammarstrom, L; Rakhmanov, M; Schlesier, M; Grimbacher, B; Peter, HH; Eibel, H; visa färre...

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