Article: article from journal or magazin.
Mutation of the BAFF furin cleavage site impairs B-cell homeostasis and antibody responses.
European Journal of Immunology
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.
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
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