MOLECULAR ANALYSIS OF MERCURY-INDUCED ANTINUCLEOLAR ANTIBODIES IN H-2(S) MICE

In H-2s mice, the administration of mercuric chloride results in the d evelopment of antinucleolar autoantibodies. These mice represent a val uable model to study the role of environmental factors in the developm ent 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 ribonucleoprotei n particles (RNP) and some (but not all) react with fibrillarin, the o nly currently characterized protein component of mammalian nucleolar R NP. Several V(H) and Vkappa genes are recurrently used by these antinu cleolar RNP mAb and their H chain CDR3 segments contain several acidic residues that may be important for binding to the cationic proteins c omposing 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.