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Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers

Citation

Figgett, WA and Deliyanti, D and Fairfax, KA and Quah, PS and Wilkinson-Berka, JL and Mackay, F, Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers, Journal of Autoimmunity, 61 pp. 9-16. ISSN 0896-8411 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 Elsevier Ltd.

DOI: doi:10.1016/j.jaut.2015.04.007

Abstract

B cell-activating factor of the TNF family (BAFF) is an essential B cell survival factor. However, high levels of BAFF promote systemic lupus erythematosus (SLE) in mice and humans. Belimumab (anti-human BAFF) limits B cell survival and is approved for use in patients with SLE. Surprisingly, the efficacy of rituximab (anti-human CD20) in SLE remains controversial, despite depleting B cells more potently than belimumab. This raises the question of whether B cell depletion is really the mechanism of action of belimumab. In BAFF transgenic mice, SLE development is T cell-independent but relies on innate activation of B cells via TLRs, and TLR expression is modulated by the BAFF receptor TACI. Here, we show that loss of TACI on B cells protected against BAFF-mediated autoimmune manifestations while preserving B cells, suggesting that loss of BAFF signaling through TACI rather than loss of B cells may underpin the effect of belimumab in the clinic. Therefore, B cell-sparing blockade of TACI may offer a more specific and safer therapeutic alternative to broad B cell depletion in SLE.

Item Details

Item Type:Refereed Article
Keywords:autoantibodies, BAFF, Lupus nephritis, systemic lupus erythematosus, TACI, TLR7
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Development, Proliferation and Death
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
UTAS Author:Fairfax, KA (Dr Kirsten Fairfax)
ID Code:134801
Year Published:2015
Web of Science® Times Cited:28
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-09-05
Last Modified:2019-10-16
Downloads:0

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