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


Figgett, WA; Deliyanti, D; Fairfax, KA; Quah, PS; Wilkinson-Berka, JL; Mackay, F
2015-05-28
J Autoimmun
Journal Article in press
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.
Elsevier
Molecular Medicine
10.1016/j.jaut.2015.04.007
26027434
Refer to copyright notice on published article.

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Creation Date 2015-06-15 09:53:25 Last Modified 2015-06-15 11:16:37