Idiotypic cross-reaction between MRL monoclonal autoantibodies with different antigen specificity

The idiotypic determinants borne by Y2, a monoclonal anti-SM antibody of MRL mouse strain origin, were investigated to elucidate mechanisms for the generation of autoantibodies. Using an ELISA assay, a rabbit anti-Y2 anti-idiotypic antiserum was tested for binding to other MRL autoantibodies to identify cross-reactive determinants. In this way, a shared idiotype was demonstrated for Y2 and 4K1, 4k1 is an IgG2bK monoclonal antibody derived from a fusion with spleen cells of an MRL-lpr/lpr mouse expressing anti-Sm. 4K1 displayed an antigenic specificity distinct from anti-Sm, however, with reactivity by fluorescent antinuclear antibody analysis to a subcellular component localized to the perinuclear region. The expression of the Y2-4K1 idiotype was assessed using a sensitive inhibition ELISA. The Y2-4K1 determinant was present in sera of MRL-lpr/lpr mice irrespective of the presence of anti-Sm. Sera of some but not all normal mouse strains also demonstrated this determinant. These results indicate that while some idiotypes may be associated with autoantibodies, they are not restricted to the autoimmune setting. This pattern of expression suggests that autoantibodies are part of larger idiotype-bearing antibody families with structural similarity to antibodies produced by normal mice. The autoimmune setting may promote the emergence of idiotype-bearing molecules with autoantibody activity and aberrant regulation.