Pathogenesis of systemic sclerosis: altered B cell function is the key linking systemic autoimmunity and tissue fibrosis

J Dermatol Sci. 2005 Jul;39(1):1-7. doi: 10.1016/j.jdermsci.2005.03.013.


Systemic sclerosis (SSc) is characterized by autoimmunity and tissue fibrosis. There is a close association between specific autoantibodies and clinical features in patients with SSc. A number of studies have demonstrated that various cytokines, such as transforming growth factor-beta, modulate the synthesis of extracellular matrix by fibroblasts. However, it is not clear as to how autoimmunity and tissue fibrosis interact with each other. Recent studies have revealed that B cells play a critical role in various systemic autoimmune disorders. CD19 is a central regulator of B cell signaling threshold, and B cells from SSc patients exhibit an increased expression of CD19 that induces SSc-specific autoantibody production in transgenic mice. Furthermore, SSc patients have intrinsic B cell abnormalities characterized by decreased but activated memory B cells, which is possibly due to CD19 overexpression. Similarly, B cells from a tight-skin mouse, a model of SSc, show augmented CD19 signaling and chronic B cell activation. Remarkably, CD19 loss results in inhibition of chronic B cell hyper-reactivity and elimination of autoantibody production, which is associated with improvement in skin fibrosis and a parallel decrease in IL-6 production by B cells. Therefore, augmented cytokine production by B cells is a potential candidate for the induction of skin sclerosis. Alternatively, B cells may influence tissue fibrosis by regulating T cell activation and cytokine production through their antigen-presenting and co-stimulatory abilities. Thus, altered B cell function may result in tissue fibrosis, as well as autoimmunity, in SSc.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, CD19 / physiology
  • Autoimmunity*
  • B-Lymphocytes / immunology*
  • Cytokines / physiology
  • Fibrosis
  • Humans
  • Lymphocyte Activation
  • Mice
  • Scleroderma, Systemic / etiology*
  • Scleroderma, Systemic / immunology
  • Scleroderma, Systemic / pathology
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Antigens, CD19
  • Cytokines