Circulating immune complexes augment severity of antibody-mediated myasthenia gravis in hypogammaglobulinemic RIIIS/J mice

Tuzun E. , SCOTT B., YANG H., WU B., GOLUSZKO E., GUIGNEAUX M., ...Daha Fazla

JOURNAL OF IMMUNOLOGY, cilt.172, ss.5743-5752, 2004 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 172 Konu: 9
  • Basım Tarihi: 2004
  • Doi Numarası: 10.4049/jimmunol.172.9.5743
  • Sayfa Sayıları: ss.5743-5752


Experimental autoimmune myasthenia gravis (EAMG) is severe in RIIIS/J mice, despite a significant B cell immunodeficiency and a massive TCR Vbeta gene deletion. Severity of EAMG in RIIIS/J mice is greater than MHC-identical (H-2(r)) 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 Vbeta genes in RIIIS/J mice, we obtained (RIIIS/J x B10.RIII)F-1 (Vbeta(b/c)) x RIIIS/J (Vbeta(c)) backcross mice using Mendelian genetic methods and immunized them with acetylcholine receptor. EAMG susceptibility was not elevated in mice with Vbeta(c) genotype having 70% Vbeta 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.