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

Bossen, C. and Tardivel, A. and Willen, L. and Fletcher, C. A. and Perroud, M. and Beermann, F. and Rolink, A. G. and Scott, M. L. and Mackay, F. and Schneider, P.. (2011) Mutation of the BAFF furin cleavage site impairs B-cell homeostasis and antibody responses. European journal of immunology, Vol. 41, H. 3. pp. 787-797.

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Official URL: http://edoc.unibas.ch/dok/A6007038

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Developmental and Molecular Immunology (Rolink)
UniBasel Contributors:Rolink, Antonius G.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Verl. Chemie
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:45
Deposited On:27 Feb 2014 15:45

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