Autoimmune ipr/lpr mice deficient in cd40 ligand: spontaneous immunoglobulin class switching with dichotomy of autoantibody responses

J. Ma, J. C. Xu, Michael P. Madaio, O. Peng, J. Zhang, I. S. Grewal, R. A. Flavell, J. Craft

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Abstract

Fas-deficient MKL/Mp-lpr/lpr mice develop a syndrome that resembles human systemic lupus erythematosus, including production of IgG autoantibodies against small nuclear ribonucleoproteins (snRNPs), double-stranded DNA, and self IgG (rheumatoid factor). To investigate the necessity for T-B cell contact in MRL autoimmunity, mice deficient in CD40 ligand (CD40L) were backcrossed onto this background, and antibody synthesis assessed. In comparison to CD40L-intact Ipr/lpr counterparts, CD40L-deficient Ipr/lpr mice had elevated levels of serum IgM and lower levels of IgG; however, a subset of animals had IgG2a and IgG2b levels similar to those found in wild type Ipr/lpr mice. Levels of both isotypes in CD40L-deficient Ipr/lpr mice were significantly greater than those found in non-autoimmune CD40L-deficient animals. ANA and IgG autoantibodies against snRNPs also arose in CD40L-deficient Ipr/lpr mice; however, they did not develop IgG rheumatoid factors or antidsDNA, and lacked histologie evidence of glomerulonephritis at age three months, in contrast to CD40L-intact Ipr/lpr animals. These results indicate that isotype switching occurs in Ipr/lpr mice deficient in CD40L, and that production of IgG autoantibodies to ribonucleoproteins is preserved, suggesting that different mechanisms may be responsible for eliciting autoantibody responses in Ipr/lpr mice.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Ma, J., Xu, J. C., Madaio, M. P., Peng, O., Zhang, J., Grewal, I. S., Flavell, R. A., & Craft, J. (1996). Autoimmune ipr/lpr mice deficient in cd40 ligand: spontaneous immunoglobulin class switching with dichotomy of autoantibody responses. FASEB Journal, 10(6).