045 Role of effector and regulatory B cells in patients with systemic sclerosis: IL-6 producing effector B cells associated with skin fibrosis

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and lung fibrosis. Over 90% of the patients with SSc are positive for autoantibodies. In addition, the serum levels of BAFF, a potent B cell stimulator, are correlated with SSc severity and activity. Thus, B cells play an important role in SSc pathogenesis. However, two opposing B cell subsets exist: effector and regulatory B cells. IL-6 producing effector B cells promote scleroderma mouse model, whereas, IL-10 producing regulatory B cells inhibit it. In the present study, we have investigated the clinical association of effector and regulatory B cells in patients with SSc. The blood levels of IL-6 producing effector B cells and IL-10 producing regulatory B cells were measured in 29 patients with SSc and 16 healthy subjects by FACS. The frequency of IL-6 producing effector B cells in blood was significantly elevated in patients with SSc (55.3 ± 12.1%) than that in healthy controls (41.9 ± 10.6%, P<0.001). In contrast, the frequency of IL-10 producing regulatory B cells in blood was significantly decreased in patients with SSc (1.4 ± 0.7%) than in healthy controls (2.0 ± 0.8%, P<0.01). With respect to SSc subtypes, the frequency of IL-6 producing effector B cells was significantly higher in patients with diffuse cutaneous SSc (severe form of SSc) than that in patients with limited cutaneous SSc (mild form of SSc). Furthermore, the frequency of IL-6 producing effector B cells positively correlated with the extent of skin fibrosis in SSc patients. The result suggested that the dysregulation of effector and regulatory B cell balance contributes to SSc pathogenesis.