Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers. (July 2015)

• Record Type: Journal Article
• Authors: Figgett, William A.; Deliyanti, Devy; Fairfax, Kirsten A.; Quah, Pin Shie; Wilkinson-Berka, Jennifer L.; Mackay, Fabienne
• Is Part Of: Journal of autoimmunity. Volume 61(2015)
• Page Start: 9
• Page End: 16
• Publication Date: 2015-07
• Subjects: BAFF -- Systemic lupus erythematosus -- TACI -- TLR7 -- Autoantibodies -- Lupus nephritis; ANA anti-nuclear autoantibodies -- APRIL a proliferation-inducing ligand -- BAFF B cell-activating factor of the TNF family -- BAFFR BAFF receptor -- BCMA B cell maturation antigen -- BM bone marrow -- C3 third component of complement -- CSR class switch recombination -- CVID common variable immunodeficiency -- Fo follicular -- GC germinal center -- GSI glomerulosclerotic index -- IC immune complex -- HEL hen egg lysozyme -- MFI mean fluorescence intensity -- MZ marginal zone -- PAS periodic acid-Schiff -- PC plasma cell -- RA rheumatoid arthritis -- RF rheumatoid factors -- RNP ribonucleoprotein -- SLE systemic lupus erythematosus -- Sm Smith antigen -- SS Sjögren's syndrome -- TACI transmembrane activator and cyclophilin ligand interactor -- Tg transgenic -- WASp Wiskott–Aldrich syndrome protein -- WT wild type; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2015.04.007
• Languages: English
• ISSNs: 0896-8411

Abstract

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. Highlights: Loss of TACI expression fully protects BAFF Tg chimera mice from SLE. TACI signalling upregulates TLR7 expression in B cells. Biologics targeting TACI may treat autoimmunity without depleting B cells.