TY - JOUR
T1 - Autoimmune ipr/lpr mice deficient in cd40 ligand
T2 - spontaneous immunoglobulin class switching with dichotomy of autoantibody responses
AU - Ma, J.
AU - Xu, J. C.
AU - Madaio, Michael P.
AU - Peng, O.
AU - Zhang, J.
AU - Grewal, I. S.
AU - Flavell, R. A.
AU - Craft, J.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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M3 - Article
AN - SCOPUS:33749128959
SN - 0892-6638
VL - 10
SP - A1441
JO - FASEB Journal
JF - FASEB Journal
IS - 6
ER -