Genetic Association Between Natural Autoantibody Responses to Histones and Dna in Murine Lupus

Abstract

Genetic regulation of the spontaneous anti-histone antibody production in systemic lupus erythematosus (SLE) was studied using the H-2-congenic and T cell receptor β chain gene complex (TCRβ)-congenic NZB and NZW strains and their crosses. We found that the original, parental H-2^d/d NZB mice produced significantly higher titers of serum IgM class anti-histone antibodies than did the congenic H-2^d/2 or H-2^Z/Z NZB mice. However, none of these three NZB strains produced IgG antibodies. The NZW strain of any H-2 haplo-type did not produce IgM and IgG anti-histone antibodies. The IgG anti-histone antibodies were produced only by H-2^d/Z heterozygous NZBxNZW Fl, but not by homozygous H-2zft or H-2d'd NZBxNZW Fl mice. In studies using (NZBxNZW) FlxNZB backcross mice, only the progeny having both H-2^d/z and NZW-type TCR β genotypes produced high amounts of IgG antibodies. There was a tight linkage between the NZW-type TCR β and the production of IgG anti-histone antibodies in TCR T-congenic NZBxNZW Fl mice. All these findings were in keeping with our preceding observations on the genetic regulation of anti-DNA antibodies in these mice and suggest that certain common mechanisms such as superantigen-mediated or common idiotope-mediated regulations may underlie the production of these two distinct autoantibodies in NZBxNZW Fl mice.

Key Words:

• Autoimmunity
• anti-histone antibody
• anti-DNA antibody
• major histocompatibility complex (MHC)
• T cell receptor β chain gene complex (TCRβ)
• NZBxNZW Fl mice