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Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers
journal contribution
posted on 2023-05-20, 06:56 authored by Figgett, WA, Deliyanti, D, Kirsten FairfaxKirsten Fairfax, Quah, PS, Wilkinson-Berka, JL, Mackay, FB 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.
History
Publication title
Journal of AutoimmunityVolume
61Pagination
9-16ISSN
0896-8411Department/School
Menzies Institute for Medical ResearchPublisher
Academic Press Ltd Elsevier Science LtdPlace of publication
24-28 Oval Rd, London, England, Nw1 7DxRights statement
Copyright 2015 Elsevier Ltd.Repository Status
- Restricted