Molecular analysis of mercury-induced antinucleolar antibodies in H-2S mice.

In H-2S mice, the administration of mercuric chloride results in the development of antinucleolar autoantibodies. These mice represent a valuable model to study the role of environmental factors in the development of systemic autoimmunity. We have obtained seven antinucleolar mAb from mercury-injected A.SW mice and characterized their specificities and V genes. All mAb immunoprecipitate the U3 and U8 ribonucleoprotein particles (RNP) and some (but not all) react with fibrillarin, the only currently characterized protein component of mammalian nucleolar RNP. Several VH and V kappa genes are recurrently used by these antinucleolar RNP mAb and their H chain CDR3 segments contain several acidic residues that may be important for binding to the cationic proteins composing the nucleolar RNP. Our results support the concept that in H-2S mice administration of mercury induces a specific loss of tolerance to nucleolar RNP.