Cover

B Cell Trophic Factors and B Cell Antagonism in Autoimmune Disease

Editor(s): Stohl W. (Los Angeles, Calif.) 
Table of Contents
Vol. 8, No. , 2005
Section title: Paper
Stohl W (ed): B Cell Trophic Factors and B Cell Antagonism in Autoimmune Disease. Curr Dir Autoimmun. Basel, Karger, 2005, vol 8, pp 55-90
(DOI:10.1159/000082087)
Paper

The CD19-CD21 Signal Transduction Complex of B Lymphocytes Regulates the Balance between Health and Autoimmune Disease: Systemic Sclerosis as a Model System

Tedder T.F.a · Poe J.C.a · Fujimoto M.b · Haas K.M.a · Sato S.c
aDepartment of Immunology, Duke University Medical Center, Durham, N.C., USA; bDepartment of Dermatology, Faculty of Medicine, University of Tokyo, Bunkyo, Tokyo, and cDepartment of Dermatology, Kanazawa University Graduate School of Medical Science, Ishikawa, Kanazawa, Japan

Abstract

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 ~ 50%, which leads to autoantibody production. Autoimmune patients with systemic sclerosis also overexpress CD19 by ~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.

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