Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers
- Author(s)
- Figgett, WA; Deliyanti, D; Fairfax, KA; Quah, PS; Wilkinson-Berka, JL; Mackay, F;
- Journal Title
- J Autoimmun
- Publication Type
- Journal Article in press
- 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.
- Publisher
- Elsevier
- Research Division(s)
- Molecular Medicine
- PubMed ID
- 26027434
- Publisher's Version
- https://doi.org/10.1016/j.jaut.2015.04.007
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-06-15 09:53:25
Last Modified: 2015-06-15 11:16:37