Specificities of IgM and IgG anti-histone H1 autoantibodies in autoimmune mice.
Autoantibodies to histone H1 represent the most common specificity among anti-histone autoantibodies in systemic autoimmune diseases. Here we analyse anti-H1 autoantibodies in mice from the following autoimmune strains: MRL/Mp-lpr/lpr, NZB and NZB x NZW/F1. Autoantibodies of the IgM isotype bind predominantly to epitopes located in the COOH-terminal domain of the H1 molecule, whereas IgG autoantibodies in the MRL/Mp-lpr/lpr and NZB strains also recognize epitopes requiring the integrity of both the COOH-terminal and the central globular domains of H1. In both of these strains, the titre of these IgG anti-H1 antibodies rises during the course of the disease. The importance of three-dimensional structure of histone H1 was attested by a significant decrease in IgG binding after cleavage of the H1 molecule within the folded globular domain. The binding of these sera to H1 variants from various species was also investigated and a strong binding of MRL/Mp-lpr/lpr sera to certain phylogenetically distant histone H1 variant molecules (sea-urchin sperm H1 and chicken erythrocyte H5) was observed. This cross-reacting binding can be explained by the presence in MRL/Mp-lpr/lpr sera of autoantibodies to H1(0), a variant found in non-dividing cells and exhibiting sequence homologies to the above mentioned variants. The significance and the possible implications of these data for the pathogenesis of autoimmunity are discussed.
Monestier
M
M
Institute of Molecular Immunology, University of Medicine and Dentistry of New Jersey, Newark.
Fasy
T M
TM
Debbas
M E
ME
Bohm
L
L
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D006657:Histones / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D010446:Peptide Fragments / Q000276:immunology; D013045:Species Specificity; D013997:Time Factors
D001323:Autoantibodies; D006657:Histones; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010446:Peptide Fragments