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BAFF 60-mer, and Differential BAFF 60-mer Dissociating Activities in Human Serum, Cord Blood and Cerebrospinal Fluid

Title: BAFF 60-mer, and Differential BAFF 60-mer Dissociating Activities in Human Serum, Cord Blood and Cerebrospinal Fluid
Authors: Mahya Eslami; Edgar Meinl; Hermann Eibel; Laure Willen; Olivier Donzé; Ottmar Distl; Holm Schneider; Daniel E. Speiser; Dimitrios Tsiantoulas; Özkan Yalkinoglu; Eileen Samy; Pascal Schneider
Source: Frontiers in Cell and Developmental Biology, Vol 8 (2020)
Publisher Information: Frontiers Media S.A.
Publication Year: 2020
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: B-cell activating factor; cerebrospinal fluid; serum; cord blood; 60-mer; atacicept; Biology (General); QH301-705.5
Description: B cell activation factor of the TNF family (BAFF/BLyS), an essential B cell survival factor of which circulating levels are elevated in several autoimmune disorders, is targeted in the clinic for the treatment of systemic lupus erythematosus (SLE). The soluble form of BAFF can exist as 3-mer, or as 60-mer that results from the ordered assembly of twenty 3-mers and that can be obtained from naturally cleaved membrane-bound BAFF or made as a recombinant protein. However, which forms of soluble BAFF exist and act in humans is unclear. In this study, BAFF 3-mer and 60-mer in biological fluids were characterized for size, activity and response to specific stimulators or inhibitors of BAFF. Human cerebrospinal fluids (CSF) from patients with multiple sclerosis and adult human sera contained exclusively BAFF 3-mer in these assays, also when BAFF concentrations were moderately SLE or highly (BAFFR-deficient individual) increased. Human sera, but not CSF, contained a high molecular weight, saturable activity that dissociated preformed recombinant BAFF 60-mer into 3-mer. This activity was lower in cord blood. Cord blood displayed BAFF levels 10-fold higher than in adults and consistently contained a fair proportion of active high molecular weight BAFF able to dissociate into 3-mer but not endowed with all properties of recombinant BAFF 60-mer. If BAFF 60-mer is produced in humans, it is dissociated, or at least attenuated in the circulation.
Document Type: article in journal/newspaper
Language: English
Relation: https://www.frontiersin.org/articles/10.3389/fcell.2020.577662/full; https://doaj.org/toc/2296-634X; https://doaj.org/article/76027ff55cba448a9c4dc593f4326ad2
DOI: 10.3389/fcell.2020.577662
Availability: https://doi.org/10.3389/fcell.2020.577662; https://doaj.org/article/76027ff55cba448a9c4dc593f4326ad2
Accession Number: edsbas.3185D72C
Database: BASE