In:
European Journal of Immunology, Wiley, Vol. 43, No. 3 ( 2013-03), p. 805-814
Abstract:
Mutations in the transmembrane activator and calcium‐modulating cyclophilin ligand interactor ( TACI ) were previously found to be associated with hypogammaglobulinemia in humans. It has been shown that proliferation inducing ligand ( APRIL ) elicits class switch recombination ( CSR ) by inducing recruitment of M y D 88 to a TACI highly conserved cytoplasmic domain ( THC ). We have identified a patient with hypogammaglobulinemia carrying a missense mutation ( S 231 R ) predicted to affect the THC . Aiming to evaluate the relevance of this novel mutation of TACI in CSR induction, we tested the ability of TACI , TLR 9, or/and CD 40 ligands to trigger CSR in naive B cells and B ‐cell lines carrying S 231 R . I g G secretion was impaired when triggered by TACI or/and TLR 9 ligands on S 231 R ‐naive B cells. Likewise, these stimuli induced less expression of activation‐induced cytidine deaminase, I ( γ ) 1‐ C ( μ ), and I ( γ ) 1‐ C ( μ ), while induction by optimal CD 40 stimulation was indistinguishable from controls. These cells also showed an impaired cooperation between TACI and TLR 9 pathways, as well as a lack of APRIL ‐mediated enhancement of CD 40 activation in suboptimal conditions. Finally, after APRIL ligation, S 231 R ‐mutated TACI failed to colocalize with M y D 88. Collectively, these results highlight the requirement of an intact M y D 88‐binding site in TACI to trigger CSR .
Type of Medium:
Online Resource
ISSN:
0014-2980
,
1521-4141
DOI:
10.1002/eji.201242945
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
1491907-2
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