Circulating Immune Complexes Augment Severity of Antibody-Mediated Myasthenia Gravis in Hypogammaglobulinemic RIIIS/J Mice

Erdem Tüzün, Benjamin G. Scott, Huan Yang, Bo Wu, Elzbieta Goluszko, Michelle Guigneaux, Stephen Higgs, Premkumar Christadoss

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Abstract

Experimental autoimmune myasthenia gravis (EAMG) is severe in RIIIS/J mice, despite a significant B cell immunodeficiency and a massive TCR Vβ gene deletion. Severity of EAMG in RIIIS/J mice is greater than MHC-identical (H-2r) B10.RIII mice, suggesting the influence of non-MHC genes as an EAMG-potentiating factor in this strain. To delineate the role of deleted TCR Vβ genes in RIIIS/J mice, we obtained (RIIIS/J × B10.RIII)F 1 (Vβb/c) × RIIIS/J (Vβc) backcross mice using Mendelian genetic methods and immunized them with acetylcholine receptor. EAMG susceptibility was not elevated in mice with Vβc genotype having 70% Vβ gene deletion. Next, we performed microarray analysis on 12,488 spleen cDNAs obtained from spleens of naive RIIIS/J and B10.RIII mice. In RIIIS/J mice, 263 cDNAs were overexpressed and 303 cDNAs were underexpressed greater than 2-fold, compared with B10.RIII mice. TCR gene expression was augmented, whereas NK receptor, C1q, and C3 gene expressions were diminished in RIIIS/J mice. RIIIS/J mice also had increased lymph node T cell counts, elevated serum anti-AChR Ab levels, and serum C3 and C1q-conjugated circulating immune complex levels. A direct correlation between increased serum C1q-conjugated circulating immune complex levels and disease severity was observed in RIIIS/J mice.

Original languageEnglish (US)
Pages (from-to)5743-5752
Number of pages10
JournalJournal of Immunology
Volume172
Issue number9
StatePublished - May 1 2004

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Myasthenia Gravis
Antigen-Antibody Complex
Antibodies
Autoimmune Experimental Myasthenia Gravis
Complementary DNA
Gene Deletion
Spleen
Serum
Immune Complex Diseases
Gene Expression
Cholinergic Receptors
Microarray Analysis
Genes
B-Lymphocytes
Cell Count
Lymph Nodes
Genotype

ASJC Scopus subject areas

  • Immunology

Cite this

Tüzün, E., Scott, B. G., Yang, H., Wu, B., Goluszko, E., Guigneaux, M., ... Christadoss, P. (2004). Circulating Immune Complexes Augment Severity of Antibody-Mediated Myasthenia Gravis in Hypogammaglobulinemic RIIIS/J Mice. Journal of Immunology, 172(9), 5743-5752.

Circulating Immune Complexes Augment Severity of Antibody-Mediated Myasthenia Gravis in Hypogammaglobulinemic RIIIS/J Mice. / Tüzün, Erdem; Scott, Benjamin G.; Yang, Huan; Wu, Bo; Goluszko, Elzbieta; Guigneaux, Michelle; Higgs, Stephen; Christadoss, Premkumar.

In: Journal of Immunology, Vol. 172, No. 9, 01.05.2004, p. 5743-5752.

Research output: Contribution to journalArticle

Tüzün, E, Scott, BG, Yang, H, Wu, B, Goluszko, E, Guigneaux, M, Higgs, S & Christadoss, P 2004, 'Circulating Immune Complexes Augment Severity of Antibody-Mediated Myasthenia Gravis in Hypogammaglobulinemic RIIIS/J Mice', Journal of Immunology, vol. 172, no. 9, pp. 5743-5752.
Tüzün E, Scott BG, Yang H, Wu B, Goluszko E, Guigneaux M et al. Circulating Immune Complexes Augment Severity of Antibody-Mediated Myasthenia Gravis in Hypogammaglobulinemic RIIIS/J Mice. Journal of Immunology. 2004 May 1;172(9):5743-5752.
Tüzün, Erdem ; Scott, Benjamin G. ; Yang, Huan ; Wu, Bo ; Goluszko, Elzbieta ; Guigneaux, Michelle ; Higgs, Stephen ; Christadoss, Premkumar. / Circulating Immune Complexes Augment Severity of Antibody-Mediated Myasthenia Gravis in Hypogammaglobulinemic RIIIS/J Mice. In: Journal of Immunology. 2004 ; Vol. 172, No. 9. pp. 5743-5752.
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