Idiotypic determinants of natural IgM antibodies that resemble self Ia antigens.

Abstract

A collection of Ig-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. One IgM antibody which reacts with the monoclonal anti-Ia.7 antibody 14-4-4S is described. The characterization of this clone (BA.N 4:4.57) revealed its anti-trinitrophenyl specificity and demonstrated specific binding to 5 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 specifically inhibited plaque formation by the hybridoma cells, and dinitrophenylglycine inhibited the reaction between the IgM antibody and anti-Ia.7 molecules. These results are interpreted 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. The importance of idiotypic mimicry with major histocompatibility complex determinants, for both the selection of natural antibody repertoires and the evolution of antibody genes is discussed.