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
DOIs
StatePublished - May 1 2004

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Tüzün, E., Scott, B. G., 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, 172(9), 5743-5752. https://doi.org/10.4049/jimmunol.172.9.5743