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

Research output: Contribution to journalArticle

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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Immunoglobulin Class Switching
CD40 Ligand
Immunoglobulin Isotypes
Autoantibodies
Immunoglobulin G
Small Nuclear Ribonucleoproteins
Animals
Rheumatoid Factor
Ribonucleoproteins
Glomerulonephritis
Autoimmunity
Systemic Lupus Erythematosus
Immunoglobulin M
B-Lymphocytes
Cells
Antibodies
DNA

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., ... Craft, J. (1996). Autoimmune ipr/lpr mice deficient in cd40 ligand: spontaneous immunoglobulin class switching with dichotomy of autoantibody responses. FASEB Journal, 10(6).

Autoimmune ipr/lpr mice deficient in cd40 ligand : spontaneous immunoglobulin class switching with dichotomy of autoantibody responses. / Ma, J.; Xu, J. C.; Madaio, Michael P.; Peng, O.; Zhang, J.; Grewal, I. S.; Flavell, R. A.; Craft, J.

In: FASEB Journal, Vol. 10, No. 6, 01.12.1996.

Research output: Contribution to journalArticle

Ma, J, Xu, JC, Madaio, MP, Peng, O, Zhang, J, Grewal, IS, Flavell, RA & Craft, J 1996, 'Autoimmune ipr/lpr mice deficient in cd40 ligand: spontaneous immunoglobulin class switching with dichotomy of autoantibody responses', FASEB Journal, vol. 10, no. 6.
Ma, J. ; Xu, J. C. ; Madaio, Michael P. ; Peng, O. ; Zhang, J. ; Grewal, I. S. ; Flavell, R. A. ; Craft, J. / Autoimmune ipr/lpr mice deficient in cd40 ligand : spontaneous immunoglobulin class switching with dichotomy of autoantibody responses. In: FASEB Journal. 1996 ; Vol. 10, No. 6.
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