Mutation of the BAFF furin cleavage site impairs B-cell homeostasis and antibody responses.

Détails

ID Serval
serval:BIB_BD399095B9AF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Mutation of the BAFF furin cleavage site impairs B-cell homeostasis and antibody responses.
Périodique
European Journal of Immunology
Auteur(s)
Bossen C., Tardivel A., Willen L., Fletcher C.A., Perroud M., Beermann F., Rolink A.G., Scott M.L., Mackay F., Schneider P.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Statut éditorial
Publié
Date de publication
2011
Volume
41
Numéro
3
Pages
787-797
Langue
anglais
Résumé
B-cell-activating factor of the TNF family (BAFF)/BLyS contributes to B-cell homeostasis and function in the periphery. BAFF is expressed as a membrane-bound protein or released by proteolytic cleavage, but the functional importance of this processing event is poorly understood. Mice expressing BAFF with a mutated furin consensus cleavage site, i.e. furin-mutant BAFF (fmBAFF), were not different from BAFF-deficient mice with regard to their B-cell populations and responses to immunization. It is however noteworthy that an alternative processing event releases some soluble BAFF in fmBAFF mice. Mild overexpression (∼ 5-fold) of fmBAFF alone generated intermediate levels of B cells without improving humoral responses to immunization. Processed BAFF was however important for B-cell homeostasis, as peripheral B-cell populations and antibody responses were readily restored by administration of soluble BAFF trimers in BAFF-deficient mice. However, the rescue of CD23 expression in B cells of BAFF-deficient mice required both soluble BAFF trimers and fmBAFF, or a polymeric form of soluble BAFF (BAFF 60-mer). These results point to a predominant role of processed BAFF for B-cell homeostasis and function, and indicate possible accessory roles for membrane-bound BAFF.
Mots-clé
Amino Acid Sequence, Animals, Antibody Formation, B-Cell Activating Factor/chemistry, B-Cell Activating Factor/deficiency, B-Lymphocytes/immunology, Base Sequence, Binding Sites/genetics, DNA Primers/genetics, Furin/chemistry, HEK293 Cells, Homeostasis, Humans, Immunoglobulins/blood, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Mutant Strains, Mice, Transgenic, Molecular Sequence Data, Mutant Proteins/chemistry, Mutant Proteins/genetics, Mutation, Protein Processing, Post-Translational, RNA, Messenger/genetics, RNA, Messenger/metabolism, Solubility
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/09/2011 10:53
Dernière modification de la notice
20/08/2019 15:31
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