[B cell abnormalities and autoantibody production in systemic sclerosis].
The pathogenetic roles of autoantibodies remain unknown in systemic sclerosis (SSc). CD19, a cell-surface critical signal transduction molecule of B lymphocytes, augments signaling through B cell antigen receptor and CD19 overexpression in mice induces various autoantibody production. Peripheral B cells from SSc patients exhibit 20%-increase in CD19 expression. Furthermore, B cells from a tight-skin (TSK) mouse, a genetic murine model of SSc, show augmented signaling through CD19. The deficiency of CD19 expression in TSK mice results in inhibition of autoantibody production, reduced skin fibrosis, and inhibition of augmented IL-6 production by splenic B cells. Collectively, a new model that could explain the relationship between autoantibody and the development of fibrosis is proposed. CD19 overexpression observed in SSc patients breaks down peripheral tolerance of B cells, which results in autoantibody production. Furthermore, it is also possible that in vivo chronic B cell activation probably due to CD19 overexpression results in the development of fibrosis through production of fibrogenic cytokines, such as IL-6. This model indicates that B cells or CD19 would be potential therapeutic targets in SSc.
Sato
Shinichi
S
Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences.
D000818:Animals; D018941:Antigens, CD19 / Q000096:biosynthesis / Q000502:physiology*; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D012595:Scleroderma, Systemic / Q000276:immunology*; D015398:Signal Transduction
D018941:Antigens, CD19; D001323:Autoantibodies; D015850:Interleukin-6; D011947:Receptors, Antigen, B-Cell