Anti-nRNP anti-nuclear antibody-secreting cells are represented in the B-lymphocyte repertoire of normal and MRL/MP-lpr/lpr lupus mice

Abstract

Spleen cells from MRL-lpr/lpr, CBA and BALB/c mice were cultured in vitro and assayed for production of anti-nuclear antibodies. Spleen cells from all species produced IgM antibodies to a nRNP (U1-RNP)-specific antigen and to double-stranded DNA (dsDNA) after stimulation with LPS. The specificity of the anti-nRNP antibodies was shown, by immunoblotting, to be directed against the 33,000 MW polypeptide of nRNP/Sm. CBA mice produced more IgM autoantibody in vitro than MRL/lpr or BALB/c mice. In contrast, IgG anti-nRNP and anti-dsDNA antibody were not produced by any of the strains. Our data show that anti-nRNP and anti-dsDNA precursor B cells are part of the normal murine immune repertoire and are not confined to the MRL/lpr strain. This suggests that the spontaneous development of anti-nRNP and anti-dsDNA antibodies associated with systemic lupus erythematosis (SLE) is dependent on clonal stimulation and removal of suppressive influences.