Requirements for prolonged suppression of an idiotypic specificity in adult mice.

The appearance of an idiotypic specificity, present in anti-p-azophenylarsonate (anti-Ar) antibodies of all immunized A/J mice, ran be suppressed in adult mice by prior administration of an IgG fraction of rabbit antiidiotypic (anti-D) antiserum; anti-Ar antibodies arise but are of different idiotype. Prolonged suppression was observed in earlier experiments, but antigen was first administered to adult mice only 2 wk or 9 wk after anti-D antibodies; subsequent escape from idiotypic suppression could have been masked by the capture of antigen by large numbers of memory cells having receptors of a different idiotype. In the present experiments antigen was first administered at intervals up to 22 wk after the antiidiotypic antibody. Suppression was maintained for 6 wk in all mice and for 5 mo in about half the mice tested. It thus appears that suppression of idiotype is less reversible if antigen is administered soon after the antiidiotypic antibody. The data suggest that escape from suppression is attributable to the generation of new precursor cells rather than to reactivation of suppressed cells. The minimum dosage of antiidiotypic IgG required for effective suppression was about 2 mg. The subcutaneous or intraperitoneal routes of inoculation of antiidiotypic IgG were equally effective. When antiidiotypic antibody was administered 3 days after antigen no suppressive effects were observed. There was partial suppression when antiidiotypic antibody was injected on the same day as the antigen. Fab' and F(ab')(2) fragments of antiidiotypic IgG had no suppressive effect. Quantitative measurements revealed no significant differences among control and suppressed mice with respect to total concentration of precipitable anti-Ar antibodies produced.

Distribution of a cross-reactive idiotypic specificity in inbred strains of mice.

The expression of an idiotype characteristic of anti-p-azophenylarsonate antibodies of all A/J mice was explored in F(1) progeny, in other inbred strains, and in congenic mice. Of the strains tested only those closely related to A/J produced antibodies with the cross-reactive idiotype (CRI). None of the mice synthesized intermediate levels of CRI. No relationship between H-2 type and idiotype was noted. Congenic mice with a strain A background but a different H-2 type produced CRI in amounts quantitatively equivalent to those of strain A mice. Conversely, the presence of the H-2 genotype of strain A on an unrelated background was not associated with the formation of CRI. Nearly all F(1) progeny of strain A mice formed CRI, indicating that failure of the other (non-A) parental strain to produce CRI is not attributable to the presence of a gene controlling the synthesis of a suppressor of CRI. NZB mice, which have the same heavy chain allotype as strain A, but are unrelated in origin, failed to produce CRI, although allotype has been shown to be linked to idiotype in congenic strains.

Evidence for the linkage of the IGC H locus to a gene controlling the idiotypic specificity of anti-p-azophenylarsonate antibodies in strain A mice.

Anti-p-azophenylarsonate (anti-Ar) antibodies elicited in all strain A/J mice tested share one or more idiotypic specificities. These specificities are also found in the anti-Ar antibodies of mice of the closely related strain, AL/N, but not in those of BALB/c mice. Anti-Ar antibodies were elicited in congenic mice in which the IgC(H) locus of AL/N mice, which controls allotypic markers in the constant regions of heavy chains, had been introgressively backcrossed for nine generations onto a BALB/c background; the mice were then rendered homozygous for the AL/N allotypic determinant. On the average, these antibodies were quantitatively equivalent, with respect to content of the cross-reactive idiotype, to those of AL/N mice. This indicates that the gene controlling the idiotype is closely linked to the IgC(H) locus. Since idiotype must be a function of V region sequences, the results suggest close linkage of V(H) and C(H) genes. The cross-reactive idiotype was found in nearly all F(1) mice (C57/BL x A/J or BALB/c x A/J) tested.

Suppression of idiotypic specificities in adult mice by administration of antiidiotypic antibody.

It has previously been shown that there are extensive idiotypic cross-reactions among antiphenylarsonate antibodies of A/J mice. The present work indicates that administration, into normal, adult A/J mice, of rabbit antiidiotypic antibody directed to A/J antiphenylarsonate antibody suppresses almost completely the subsequent production of antibody of the corresponding idiotype. No effect was noted on the formation of antibodies to the protein carrier or of antiphenylarsonate antibody of a different idiotype. The data are consistent with central suppression of production of the idiotypic antibody mediated through interaction with immunoglobulin receptors on lymphocytes.