An important role for B-cell activation factor and B cells in the pathogenesis of Sjogren's syndrome

Purpose of review This review provides an update on the specific, strong association between dysregulated production of the cytokine B-cell activation factor and Sjogren's syndrome, and offers new perspectives on potential pathogenic mechanisms. Recent findings Excess B-cell activation factor in mice triggers Sjogren's syndrome-like symptoms, and elevated serum B-cell activation factor in humans correlates with Sjogren'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 disorder in inflamed tissues. Summary Recent data have demonstrated the critical role of activation factor and B cells in the pathogenesis of Sjogren's syndrome, and its association with B lymphomas. Morreover, B-cell depleting treatments have confirmed the critical role of B cells in Sjogren'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.