Journal article

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

WA Figgett, D Deliyanti, KA Fairfax, PS Quah, JL Wilkinson-Berka, F Mackay

Journal of Autoimmunity | Published : 2015

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. H..

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Grants

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council and Victorian State Government Operational Infrastructure Support. JW-B and FM are Senior Research Fellows of the NHMRC. We thank M. Hibbs, F. Vincent and E. McAllister for review of the manuscript. We thank M. Le Page, Z. Nasa, M. Fuchsberger, M. Bijker, H. McGuire, R. Stokes, A. Nguyen, T. Nguyen, and J. Kang for technical assistance. The authors acknowledge the facilities and scientific and technical assistance of the Monash Animal Research Platform (MARP), Monash Histology Platform, Monash Micro Imaging, and the Monash AMREP Flow Cytometry facility.