B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis.

Published

Journal Article

Systemic sclerosis (scleroderma) is an autoimmune disease characterized by excessive extracellular matrix deposition in the skin. A direct role for B lymphocytes in disease development or progression has remained controversial, although autoantibody production is a feature of this disease. To address this issue, skin sclerosis and autoimmunity were assessed in tight-skin mice, a genetic model of human systemic sclerosis, after circulating and tissue B-cell depletion using an anti-mouse CD20 monoclonal antibody before (day 3 after birth) and after disease development (day 56). CD20 monoclonal antibody treatment (10 to 20 microg) depleted the majority (85 to 99%) of circulating and tissue B cells in newborn and adult tight-skin mice by days 56 and 112, respectively. B-cell depletion in newborn tight-skin mice significantly suppressed (approximately 43%) the development of skin fibrosis, autoantibody production, and hypergammaglobulinemia. B-cell depletion also restored a more normal balance between Th1 and Th2 cytokine mRNA expression in the skin. By contrast, B-cell depletion did not affect skin fibrosis, hypergammaglobulinemia, and autoantibody levels in adult mice with established disease. Thereby, B-cell depletion during disease onset suppressed skin fibrosis, indicating that B cells contribute to the initiation of systemic sclerosis pathogenesis in tight-skin mice but are not required for disease maintenance.

Full Text

Duke Authors

Cited Authors

  • Hasegawa, M; Hamaguchi, Y; Yanaba, K; Bouaziz, J-D; Uchida, J; Fujimoto, M; Matsushita, T; Matsushita, Y; Horikawa, M; Komura, K; Takehara, K; Sato, S; Tedder, TF

Published Date

  • September 2006

Published In

Volume / Issue

  • 169 / 3

Start / End Page

  • 954 - 966

PubMed ID

  • 16936269

Pubmed Central ID

  • 16936269

International Standard Serial Number (ISSN)

  • 0002-9440

Digital Object Identifier (DOI)

  • 10.2353/ajpath.2006.060205

Language

  • eng

Conference Location

  • United States