Partial expression of the lpr locus in the heterozygous state: presence of autoantibodies

Abstract

B6 mice heterozygous at the lpr locus (B6 +/lpr and B6 lpr/+) were compared with lpr homozygous mice (B6 lpr/lpr) and control mice (B6 +/+) for levels of serum immunoglobulin (Ig), presence of autoantibodies and rate of B-cell membrane immunoglobulin (mIg) capping. The total serum Ig levels in B6 +/lpr and B6 lpr/+ mice remained much below the high titres found in B6 lpr/lpr mice, and were close to the titres found in B6 +/+ mice. However, the presence of anti-single-stranded (ss) DNA antibodies and of anti-nuclear antibodies (ANA) was detected in most B6 +/lpr and B6 lpr/+ mice, although less frequently and in lower titres than in B6 lpr/lpr mice. The rate of mIg capping was higher in B6 +/lpr and B6 lpr/+ mice than in B6 +/+ mice, but the acceleration of the capping process remained inferior to the one found in B6 lpr/lpr mice. Therefore, the lpr locus is not totally recessive: some B-cell hyperactivity is expressed in the heterozygous state. This is in contrast with its lack of expression at the level of lympho-proliferation of the lpr-characteristic T-cell subset: none of the lpr heterozygous B6 mice displayed detectable lymphadenopathy.