Specific Inhibition of Plaque Formation to Phosphorylcholine by Antibody against Antibody

Williams et al.(1) in a study of monoclonal IgM cold agglutinins noted that antisera to different cold agglutinins possessed specificity not only for antigenic determinants unique to the individual proteins but also for determinants that were shared by cold agglutinins from a number of individuals . This phenomenon of shared or cross-idiotypy among immunoglobulins with similar specificity also has been demonstrated for human proteins with anti-7-globulin activity (2) and among rabbit (3, 4) and mouse (5) antibodies to streptococcal group carbohydrates . In most instances the proteins exhibiting cross-idiotypic reactions had similar, but not necessarily identical, combining sites, and the idiotypic determinant shared by them was associated with the combining site (2, 5-8) . Support for the structural similarity of antibodies with similar specificity and shared idiotypy has been provided by recent findings showing that IgM cold agglutinins, anti-y-globulins (9, 11), or rabbit antibodies to streptococcal group C carbohydrate (7) have strikingly similar heavy and/or light chains .Previous studies from our laboratory have demonstrated a remarkable similarity in the combining sites of mouse antibodies to phosphorylcholine (PC)' regardless of the genetic background of the mice. The antibodies from the mouse strains tested possessed indistinguishable binding specificities for a number of choline analogues (12) and had identical binding-site antigenic determinants (13) . This suggests a striking conservation of the binding site region of mouse anti-PC antibodies, even though differences have been shown to exist in other portions of the variable region (14-16) . In contrast, it was shown (17) that three PC-binding myeloma proteins that differed in combining specificity (18), as well as in idiotypes (19) and in light chains (17), have heavy chain sequences which are virtually identical through the first hypervariable region . These findings *

Section: Discussionmentioning

confidence: 99%

Clonal nature of the immune response to phosphorylcholine (PC). V. Cross-idiotypic specificity among heavy chains of murine anti-PC antibodies and PC-binding myeloma proteins.

Claflin¹,

Davie²

1975

“…Suppression was similar when challenge with H8 was begun after two or three immunizations with Pc. 2 The ARA raised in A/He mice against H8 effectively suppressed immunization to Pc in both A/He and BALB/c mice. For example, 0.2 ml of ARA was given intraperitoneally to each of four normal adult BALB/c mice, and to each of four normal A/He mice 24 h before i.v.…”

Section: Resultsmentioning

confidence: 99%

“…Complementary idiotypes combine to quench or neutralize the activities of each other; thus, one complementary antibody can be used to inhibit hemolytic plaque formation by cells releasing the other antibody (2). The emergence of clones producing antibody of a different idiotype is revealed by the failure of a standard or "reference" complementary antibody to inhibit plaque formation by cells releasing the different idiotype (3)(4)(5).…”

mentioning

confidence: 99%

Simultaneous complementary idiotypic responses: absence of reciprocal regulation

Da¹,

Miller²,

Lorbach³

1978

Complementary antibodies, i.e. antibodies having combining site structures which are at least partially directed against each other, were induced in A/He mice by immunization with phosphorylcholine (Pc) coupled to keyhole limpet hemocyanin or with the Pc-binding IgA myeloma protein, HOPC-8 (H8). Both responses were monitored by enumerating plaque-forming cells and assaying serum antibody levels to Pc and H8. Prior immunization with H8 markedly suppressed subsequent immunization with Pc and vice versa; neither plaque-forming cell response was diminished, however, when mice were immunized simultaneously with Pc and H8. Experiments were designed to determine if the absence of reciprocal regulation was due to change in idiotypes. This was determined by measuring inhibition of plaque formation using complementary antibody. Plaque formation by cells was equally inhibited by high dilutions of the appropriate complementary antibody whether cells were from mice immunized with one, the other, or both antigens. Thus, the absence of regulation could not be accounted for by emergence of different idiotypes. Interestingly, sera from mice immunized to have high responses to both antigens were relatively ineffective in inhibiting plaque formation or suppressing immunization to Pc. However, such sera contained complexes of the complementary antibodies; apparently antibody to Pc in such sera quenches or neutralizes the activity of anti-H8 antibody. But the formation of complexes, at least measurable levels of circulating complexes, must be a result rather than the cause for the absence of reciprocal regulation, since regulation was also absent when immunization to Pc was manipulated so that responses were too low to result in detectable levels of circulating antibody to Pc. It is proposed that simultaneous complementary responses may occur in nature to other antigens and antibodies, and that such simultaneous responses may cause pathologic changes.

“…It does not possess, however, the idiotypic determinant recognized by A anti-H8. 5 The fact that the H88 idiotype is present on anti-PC antibodies of all mice, and thus can be considered a species-specific idiotype, clearly distinguishes the immune response to PC from other antibody responses. In systems such as the antistreptococcal and anti-p-azohapten antibody response idiotypic cross reactions are not usually observed except among selectively bred rabbits (18,22,24) or within an inbred strain of mice (20,21,23,25).…”

Section: Extent Of Shared Idiotypy On Hopc 8 and Mouse Anti-pc Antibomentioning

confidence: 99%

“…Idiotypic Specificities on Mouse Anti-PC Antibody.--Using mouse (A or CE) antisera, studies in several laboratories (2,(5)(6)(7) have demonstrated that anti-PC antibodies raised in BALB/c but not A or CE mice share idiotypic specificities with HOPC 8. We have shown that the rabbit anti-HOPC 8 antiserum, R2-anti-H88, recognized antigenic determinant(s) on BALB/c anti-PC antibodies.…”

Section: Specificity Of Idiotypic Antisera For Itopc 8--the Isolatiomentioning

confidence: 99%

Clonal Nature of the Immune Response to Phosphorylcholine

Claflin

Davie

1974

102

Studies of the binding characteristics for a number of choline analogues have revealed that antiphosphorylcholine (PC) 1 antibodies from 15 different inbred mouse strains which differ in histocompatibility and heavy-chain allotype are remarkably restricted and show the same binding specificity as a PC-binding myeloma protein, HOPC 8. 2' 3 This suggests that the anti-PC antibodies of all mice possess similar binding sites for PC. Indeed Cosenza and KShler (5) and others (2, 6, 7) using mouse antimouse idiotypic antisera have dearly demonstrated that anti-PC antibody from BALB/c possesses antigenic determinants shared by HOPC 8. Paradoxically however, antibodies from other strains, such as C57BL/6, A, and CE mice (2, 5-7), do not have this idiotypic specificity even though their antibody specificity cannot be distinguished from that of BALB/c. These studies indicate that variable-region determinants differ in the anti-PC antibodies of different strains of mice, but since the hapten inhibition of binding to idiotype was not studied, it is not dear that these idiotypic differences lie in the binding region. This consideration is crucial to the analysis of antibody combining-site diversity since selective pressures exerted on binding site and nonbinding site regions may be different.