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

Abstract

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 ( approximately 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.

Authors Bossen, C.; Tardivel, A.; Willen, L.; Fletcher, C. A.; Perroud, M.; Beermann, F.; Rolink, A. G.; Scott, M. L.; Mackay, F.; Schneider, P.
Publisher Name EUR J IMMUNOL
Published Date 2011-03-15 00:00:00
Published Volume 41
Published Issue 3
Published Pages 787-97
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21287546
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?10969_11343/EurJournImmunol.pdf