An important role for B-cell activation factor and B cells in the pathogenesis of Sjögren's syndrome.
OBJECTIVE
This review provides an update on the specific, strong association between dysregulated production of the cytokine B-cell activation factor and Sjögren's syndrome, and offers new perspectives on potential pathogenic mechanisms.


RESULTS
Excess B-cell activation factor in mice triggers Sjögren's syndrome-like symptoms, and elevated serum B-cell activation factor in humans correlates with Sjögren's syndrome. B-cell activation factor is produced locally by activated monocytes, T cells and dendritic cells, and by epithelial cells and infiltrating B cells. Moreover, recent data in humans suggest that the innate immune system plays a role as an initiator of immune disorders in inflamed tissues.


CONCLUSIONS
Recent data have demonstrated the critical role of B-cell activation factor and B cells in the pathogenesis of Sjögren's syndrome, and its association with B lymphomas. Moreover, B-cell depleting treatments have confirmed the critical role of B cells in Sjögren's syndrome. Excess B-cell activation factor possibly corrupts B-cell tolerance and allows the emergence of self-reactive B cells that efficiently present antigen to T cells. In addition, B-cell activation factor may stimulate T-cell independent activation of B cells via Toll-like receptors; this recently identified mechanism could also play a separate, detrimental role in autoimmunity.
Mackay
Fabienne
F
The Autoimmunity Research Unit, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia. f.mackay@garvan.org.au
Groom
Joanna R
JR
Tangye
Stuart G
SG
D000818:Animals; D053264:B-Cell Activating Factor / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D019948:Receptors, Interleukin-4 / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology / Q000503:physiopathology*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology
D053264:B-Cell Activating Factor; D019948:Receptors, Interleukin-4; C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13