Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by excessive fibrosis of the skin and internal organ. FcγRIIB, a low-affinity receptor for the Fc fragment of IgG, is expressed on the surface of several leukocyte subsets and functions in negative feedback pathways to down-regulate B cell antigen receptor signaling. To elucidate the role of FcγRIIB in the development of fibrosis, a murine bleomycin (BLM)-induced scleroderma model was examined in mice lacking FcγRIIB (FcγRIIB-/- mice). FcγRIIB expression on B cells of patients with SSc and healthy controls was also examined. The severity of fibrosis in the skin and lungs was significantly greater in BLM-treated FcγRIIB-/- mice than in BLM-treated wild-type (WT) mice. In the skin of BLM-treated mice, the numbers of CD8+ T cells, F4/80+ macrophages, MPO+ neutrophils, NK1.1+NK cells, and B220+ B cells were significantly higher in FcγRIIB-/- mice than in WT mice. The expression of TNF-α and IL-1β was significantly higher in FcγRIIB-/- mice than in WT mice as was the expression of ICAM-1, CXCL2, and CCL3 in the affected skin. Adoptive transfer of splenic leukocytes from FcγRIIB-/- mice into WT mice resulted in exacerbated skin and lung fibrosis compared with WT mice without adoptive transfer. These results indicate that FcγRIIB plays an inhibitory role in skin and lung fibrosis. On the other hand, the expression levels of FcγRIIB on SSc naïve and DN memory B cells were significantly increased compared to healthy controls. Increased FcγRIIB expression levels on double negative memory B cells were associated with presence of interstitial lung disease. Thus, SSc B cells may exhibit compensatory elevation in the expression levels of FcγRIIB in order to suppress the abnormal activation of B cells.

ESDR028 - A role for FcγRIIB in systemic sclerosis

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.