B lymphocytes: shedding new light on the pathogenesis of systemic sclerosis.
Systemic sclerosis (SSc) is a connective tissue disease characterized by autoimmunity and tissue fibrosis. In patients with SSc, there is a close association between the presence of specific autoantibodies and the development of clinical features. Although it is known that cytokines, including transforming growth factor-beta, can modulate the synthesis of extracellular matrix by fibroblasts, it is not clear how autoimmunity and tissue fibrosis are interrelated. Several recent lines of evidence indicate a potential role for B cells in the development of SSc. CD19 is a critical regulator of B-cell signaling thresholds, and B cells from SSc patients exhibit increased expression of CD19, a molecule that induces SSc-specific autoantibody production in transgenic mice. Both SSc patients and tight-skin mice, a genetic model of SSc, have intrinsic B-cell abnormalities characterized by chronic B-cell activation. Remarkably, CD19 loss or B-cell depletion using antimouse CD20 antibody suppresses the development of skin hyperplasia and autoimmunity in tight-skin mice. Additionally, a recent study revealed a possible beneficial effect of antihuman CD20 antibody (rituximab) therapy for SSc patients. As B cells have a variety of functions, further investigation into the pathogenic roles of B cells, as well as trials of B-cell-targeting therapies, may shed new light on the pathogenesis of SSc.
Hasegawa
Minoru
M
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan. minoruha@derma.m.kanazawa-u.ac.jp
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D001323:Autoantibodies / Q000009:adverse effects / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005355:Fibrosis; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D000069283:Rituximab; D012595:Scleroderma, Systemic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000276:immunology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D018951:Antigens, CD20; D001323:Autoantibodies; D016207:Cytokines; D016212:Transforming Growth Factor beta; D000069283:Rituximab