Mutation of the BAFF furin cleavage site impairs B-cell homeostasis and antibody responses - PubMed (original) (raw)

doi: 10.1002/eji.201040591. Epub 2011 Feb 1.

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• PMID: 21287546
• DOI: 10.1002/eji.201040591

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

Claudia Bossen et al. Eur J Immunol. 2011 Mar.

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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 (∼ 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.

Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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