AUTOIMMUNE LPR LPR MICE DEFICIENT IN CD40 LIGAND - SPONTANEOUS IG CLASS SWITCHING WITH DICHOTOMY OF AUTOANTIBODY RESPONSES/

Fas-deficient MRL/Mp-lpr/lpr mice develop a syndrome that resembles hu man systemic lupus erythematosus, including production of IgG autoanti bodies against small nuclear ribonucleoproteins (snRNPs), dsDNA, and s elf IgG (rheumatoid factor). To investigate the necessity for T-B cell contact in MRL autoimmunity, mice deficient in CD40 ligand (CD40L) we re backcrossed onto this background, and Ab synthesis was assessed. In comparison to their CD40L-intact lpr/lpr counterparts, CD40L-deficien t lpr/lpr mice had elevated levels of serum IgM and lower levels of Ig G; however, a subset of animals had IgG2a, and to a lesser extent, IgG 2b levels similar to those found in wild-type lpr/lpr mice. Levels of both isotypes in CD40L-deficient lpr/lpr mice were significantly great er than those found in nonautoimmune CD40L-deficient animals. IgG auto antibodies, including those directed against small nuclear ribonucleop roteins, also arose in CD40L-deficient lpr/lpr mice; however, they did not develop IgG rheumatoid factors or anti-dsDNA, and lacked histolog ic evidence of overt glomerulonephritis at age 3 mo, in contrast to CD 40L-intact lpr/lpr animals. These results indicate that isotype switch ing occurs in lpr/lpr mice deficient in CD40L, and that production of IgG autoantibodies to ribonucleoproteins is at least partially preserv ed. They also suggest that different mechanisms may be responsible for eliciting autoantibody responses in lpr/lpr mice.