How does BAFF activate B cells in patients with autoimmune diseases?

Yoshimoto and colleagues [1] demonstrate that peri pheral monocytes from patients with Sjögren's syndrome (SS) produce signifi cantly higher amounts of the cytokines B cell-activating factor (BAFF) (also called B-lympho cyte stimulator, or BlyS) and interleukin-6 (IL-6) in compari son with normal monocytes. Increased expression of BAFF might explain pathogenic B-cell activation in several systemic autoimmune diseases (reviewed in [2]). Interestingly , autoreactive B cells depend more on BAFF for survival than do alloreactive B cells. BAFF involvement in the pathogenesis of autoimmune diseases is well illustrated in BAFF-transgenic mice, which exhibit an auto-immune disease mimicking systemic lupus erythemato sus (SLE) and primary Sjögren's syndrome (pSS) as well as a twofold increase in frequency of B-cell lymphoma [3]. In humans, an increased serum level of BAFF was reported in diff erent autoimmune diseases, and fi ndings concerning SLE and pSS were more consistent (reviewed in [2]). Recent fi ndings showed that BAFF could be expressed and secreted by resident cell targets of autoimmunity after stimulation with diff erent cytokines: synoviocytes in rheumatoid arthritis, astrocytes in multiple sclerosis, and epithelial cells in pSS [4]. Moreover, in the context of autoimmunity, BAFF could be secreted by T [5] and B [6] lymphocytes. However, the main sources of BAFF are myeloid cells and, especially, blood monocytes, myeloid dendritic cells, and macrophages [7]. It has been suggested that monocytes from patients with autoimmune diseases were more susceptible to BAFF expression and secretion after stimulation with type 1 interferon (IFN) than those from healthy controls [8]. Yoshimoto and colleagues [1] add an important point to this discussion by emphasizing the role of monocytes in the overproduction of BAFF in autoimmunity. Th e authors demonstrate that peripheral pSS monocytes produce signi fi cantly higher amounts of BAFF and IL-6 in comparison with normal monocytes. Th is diff erence exists at baseline and is amplifi ed after stimulation with type 2 IFN, IFN-γ. Increased IL-6 secretion is partially suppressed by an anti-BAFF antibody, suggesting that signal transduction pathways mediated by BAFF are impli cated in the regulation of IL-6 production by monocytes. Lastly, the authors fi nd elevated expression levels of BAFF-R and diff erent transcription factors regulat ing IL-6 in pSS monocytes. We have three comments in regard to this interesting study. 1. The diff erential roles of type 1 and type 2 IFN in autoimmune diseases Like lupus, pSS is considered to be a type …