Idiotypic determinants of natural IgM antibodies that resemble self Ia antigens.
A collection of immunoglobulin-secreting B-cell hybridomas was derived from normal neonatal BALB/c spleen and searched for reactivity against a panel of monoclonal anti-H-2 antibodies. We describe here one IgM antibody which was found to react with the monoclonal anti-Ia.7 antibody 14-4-4S. The characterization of this clone (BA.N 4:4.57) revealed its anti-trinitrophenyl specificity and demonstrated specific binding to five different monoclonal anti-Ia.7 antibodies but not to other anti-H-2 antibodies. The variable region specificity of these interactions was shown by the use of pepsin Fab fragments of the IgM antibody. Anti-Ia.7 antibodies were shown to specifically inhibit plaque formation by the hybridoma cells, and dinitrophenylglycine was shown to inhibit the reaction between the IgM antibody and anti-Ia.7 molecules. We interpret these results as to indicate that BA.N 4:4.57 expresses an idiotope or idiotopes which mimic Ia.7 determinants. This idiotypic family is naturally expressed in both newborn and adult BALB/c mice, as shown by the presence in normal serum of IgM molecules that specifically react with the F(ab')2 fragment of the 14-4-4S antibody. We speculate on the importance of idiotypic mimicry with major histocompatibility complex determinants, for both the selection of natural antibody repertoires and the evolution of antibody genes.
D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis*; D006462:Hemolytic Plaque Technique; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes / Q000032:analysis*; D007075:Immunoglobulin M / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011863:Radioimmunoassay
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M