Pierre Sanchez

Immune response induced by a single or several syngeneic monoclonal antiABPC48 antiidiotypic antibodies: No predominant coexpression of ABPC48 idiotopes

BALB/c mice were immunized with monoclonal BALB/c antibodies IDA10, IDA16 and IDA17 raised against the BALB/c ABPC48 myeloma protein. Several procedures of immunization--copolymers with lipopolysaccharide or keyhole limpet hemocyanin, simultaneous or sequential injections of different IDAs--were performed in an attempt to orient the immune response towards the production of ABPC48-like idiotypes. We used a binding assay which identifies two idiotopes on the same molecule to measure the population of antibodies induced in these responses. The expression of ABPC48 cross-reactive idiotypes in immune sera was analyzed. The results show that, with all immunization protocols, immune responses to different monoclonal antiidiotypic antibodies are mostly independent of each other: the coexpression of ABPC48 idiotopes, either private or recurrent on the induced antibodies, is rarely found; it makes it difficult to discriminate by a serological approach between cross-reactive idiotypes and anti-antiidiotypic antibodies. We discuss the interest of combining molecular and serological approaches to identify these two populations of antibodies.

The expression of a private idiotope requires pretreatment with noncomplementary anti-idiotypic antibodies

The levan-binding ABPC48 myeloma protein is characterized by 3 idiotopes, (Ids), defined by 3 syngeneic monoclonal anti-idiotypic antibodies (IDA 10, IDA 16 and IDA 17). When BALB/c mice are immunized with levan, they produce anti-levan antibodies, some of which carry the Id 10 and Id 16 but not the Id 17 determinants. In the present study, we attempted to induce the synthesis of Id 17 positive anti-levan molecules. We found that immunization with IDA 17 antibodies alone was ineffective in inducing an Id 17 positive anti-levan response. By contrast, successive immunizations with IDA 10, IDA 16 and IDA 17 antibodies resulted in the synthesis of Id 17 positive anti-levan immunoglobulins. The synthesis of these molecules was concommitant with the induction of Id 10 and Id 16 positive anti-levan antibodies. Thus our data suggest that the Id 17 determinant on anti-levan antibodies is coexpressed with Id 10 and Id 16, and that successive anti-idiotypic treatment may result in the selective expansion of rare ABPC48 cross-reactive idiotype B-cell clone precursors.

Specificity and idiotypic analysis of monoclonal antibodies directed against the MOPC460 idiotype

Eight syngeneic anti-idiotypic hybridomas (IDMs) have been obtained against the BALB/c myeloma protein MOPC460 which displays anti-TNP activity. The study of their anti-idiotype specificity allowed us to distinguish them into two groups which define the presence of at least two idiotypic determinants or idiotopes in the MOPC460 idiotype. The biochemical analysis of the monoclonal antibodies is consistent with this dichotomy. This analysis, in fact, showed a striking correlation between anti-idiotypic specificity and biochemical characteristics of the monoclonal antibodies. Consequently, the idiotypic specificities of three of these hybridomas were studied. In accordance with what is expected, our results clearly indicate a strong idiotypic similarity for hybridomas belonging to the same group and a lack of idiotypic cross-reactivity.

Murine anti-TNP antibodies positive for either λ1 OR λ2 light chains express common idiotypic determinants

Abstract Although the lambda-bearing antibodies represent only 5% of the total mouse serum immunoglobulins, some antigens such as B1355 dextran (α(1–3)Dex), the 4-hydroxy-3-nitrophenyl acetyl (NP) and 2,4-dinitro or 2,4,6-trinitrophenyl (DNP/TNP) antigens can induce lambda-positive immune responses. In contrast to the lambda antibody response against α(1–3)Dex and NP antigens which is restricted to the λ1 isotype it was shown that the response to the DNP (or TNP) antigen uses λ1and λ2 and λ3 isotypes. The idiotypy of the α(1–3)Dex and NP systems has been well characterized contrary to that of the lambda-positive anti-TNP/DNP response which has been poorly studied. In this paper, we describe two idiotopes (Id C19-3 and Id D1 1–2) shared by two BALB/c monoclonal anti-TNP antibodies (TNP5 and TNP9) which, respectively, use the λ1 and λ2 light chains. These idiotopes were independently expressed on other monoclonal anti-TNP/DNP antibodies and appear to require the use of a unique V H gene associated with a particular V λ region. After TNP-Ficoll immunization, BALB/c mice recurrently express both idiotopes on λ1 and (λ2+λ3) anti-TNP antibodies. In addition, all the mouse strains immunized against TNP-Ficoll give a λ1- and (λ2 + λ3)-positive immune response with the exception of SJL and SJA strains which present a deficit for the expression of λ1 light chain. The expression of Id C19-3 was restricted to the strains with the Igh-V a allotypic haplotype (including SJA) whereas the Id D11-2 was extensively expressed in the various strains.