Function, occurrence and inhibition of different forms of BAFF

B cell activating factor (BAFF or BLyS), an important cytokine for B cell survival and humoral immune responses, is targeted in the clinic for the treatment of systemic lupus erythematosus. This review focuses on the structure, function and inhibition profiles of membrane-bound BAFF, soluble BAFF 3-...

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Bibliographic Details
Published in:Current opinion in immunology 2021-08, Vol.71, p.75-80
Main Authors: Eslami, Mahya, Schneider, Pascal
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal, Humanized - pharmacology
B-Cell Activating Factor - antagonists & inhibitors
B-Cell Activating Factor - immunology
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
Humans
Immunosuppressive Agents - pharmacology
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Summary:B cell activating factor (BAFF or BLyS), an important cytokine for B cell survival and humoral immune responses, is targeted in the clinic for the treatment of systemic lupus erythematosus. This review focuses on the structure, function and inhibition profiles of membrane-bound BAFF, soluble BAFF 3-mer and soluble BAFF 60-mer, all of which have distinct properties. BAFF contains a loop region not required for receptor binding but essential for receptor activation via promotion of BAFF-to-BAFF contacts. This loop region additionally allows formation of BAFF 60-mer, in which epitopes of the BAFF inhibitor belimumab are inaccessible. If 60-mer forms in humans, it is predicted to be short-lived and to act locally because adult serum contains a BAFF 60-mer dissociating activity. Cord blood contains elevated levels of BAFF, part of which displays attributes of 60-mer, suggesting a role for this form of BAFF in the development of foetal or neonate B cells.
ISSN:0952-7915
1879-0372
DOI:10.1016/j.coi.2021.06.009