The CD19-CD21 signal transduction complex of B lymphocytes regulates the balance between health and autoimmune disease: systemic sclerosis as a model system.

Published

Journal Article (Review)

Cell-surface CD19 functions as a general rheostat for defining intrinsic and antigen receptor-induced signaling thresholds critical for clonal expansion of the B cell pool and humoral immunity. CD19 also governs B cell responses initiated through the CD21 receptor, where complement C3d binding to CD21 links humoral immune responses with the innate immune system. Alterations in this signaling pathway can predispose mice and humans to autoantibody production and systemic autoimmunity. Transgenic mice that overexpress CD19 by 20-170% lose tolerance and generate autoantibodies. Likewise, B cells from CD21-deficient mice overexpress CD19 by approximately 50%, which leads to autoantibody production. Autoimmune patients with systemic sclerosis also overexpress CD19 by approximately 20%, which may contribute to their intrinsic B cell abnormalities and autoantibody production. Thus, chronic B cell activation resulting from augmented CD19 expression or signaling through the CD19 pathway may reveal a prototype autoimmune disease susceptibility pathway in mice and humans.

Full Text

Duke Authors

Cited Authors

  • Tedder, TF; Poe, JC; Fujimoto, M; Haas, KM; Sato, S

Published Date

  • January 2005

Published In

Volume / Issue

  • 8 /

Start / End Page

  • 55 - 90

PubMed ID

  • 15564717

Pubmed Central ID

  • 15564717

Electronic International Standard Serial Number (EISSN)

  • 1662-2936

International Standard Serial Number (ISSN)

  • 1422-2132

Digital Object Identifier (DOI)

  • 10.1159/000082087

Language

  • eng