Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination. - Archive ouverte HAL Access content directly
Journal Articles European Journal of Immunology Year : 2013

Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination.

(1) , (2) , (1) , (1) , (2) , (3) , (2) , (1)
1
2
3

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 MyD88 to a TACI highly conserved cytoplasmic domain (THC). We have identified a patient with hypogammaglobulinemia carrying a missense mutation (S231R) 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, TLR9, or/and CD40 ligands to trigger CSR in naive B cells and B-cell lines carrying S231R. IgG secretion was impaired when triggered by TACI or/and TLR9 ligands on S231R-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 CD40 stimulation was indistinguishable from controls. These cells also showed an impaired cooperation between TACI and TLR9 pathways, as well as a lack of APRIL-mediated enhancement of CD40 activation in suboptimal conditions. Finally, after APRIL ligation, S231R-mutated TACI failed to colocalize with MyD88. Collectively, these results highlight the requirement of an intact MyD88-binding site in TACI to trigger CSR.
Embargoed file
Embargoed file
Ne sera jamais visible
Loading...

Dates and versions

pasteur-00845824 , version 1 (17-07-2013)

Identifiers

Cite

Maria B Almejun, Montserrat Cols, Marta Zelazko, Matias Oleastro, Andrea Cerutti, et al.. Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination.. European Journal of Immunology, 2013, 43 (3), pp.805-14. ⟨10.1002/eji.201242945⟩. ⟨pasteur-00845824⟩
24 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More