Induction of a cross-reactive idiotype dextran-positive antibody response in two IgH-Cb mouse strains treated with anti-J558 cross-reactive idiotype antibodies.

Abstract

The effect of IdX-specific rabbit and allogeneic antiidiotype antibodies (Ab2) was investigated in vivo in Igh-Cb mouse strains with respect to the induction of a cross-reactive idiotype (IdX)-positive anti-alpha (1-3) Dextran (Dex) response. These C.B20 and C57Bl/6 mice have an allotype-linked incapacity to respond with IdX-positive anti-alpha (1-3) Dex antibodies upon conventional immunization with Dex B1355. 7 d after the rabbit Ab2 injections, IdX-positive Ig (Ab3) and IdX-positive anti-alpha (1-3) Dex antibodies (Ab1') were detected in the sera of each tested mouse. The affinity-purified Ab1' were idiotypically indistinguishable from reference BALB/c IdX-positive myeloma proteins and BALB/c anti-alpha (1-3) Dex antibodies (Ab1) in a competitive inhibition radioimmunoassay, while Ab3 Ig appeared idiotypically deficient and did not bind to Dex. The response to the alpha (1-6) linkage of Dex was not affected in these mice. A large fraction of the Ab1' and Ab3 responses of both mouse strains were of the IgG1 class. The Ab1' antibodies differed from BALB/c Ab1 by lower relative binding to five of eight tested Dex, and by expressing the Igh4b allotype determinants on the IgG1 antibodies. This study identifies the products of a VHDex gene that appears to be under regulatory control in the Ighb mice. Its association with the b haplotype suggests that this gene may differ structurally from the BALB/c VHDex gene.

Idiotypic vaccines and infectious diseases

“…For example, strains of mice expressing different allotypes produce distinct Ab1 characterized by different idiotypes in response to a given antigenic challenge (39). Those allotyperestricted idiotypes can be expressed in some strains and be part of the silent repertoire of other strains (44,49). Priming with an anti-idiotypic antibody can activate silent B-cell clones (2, 44, 49, 69).…”

“…Nevertheless, it can be argued that this idiotype is part of the silent repertoire of those mice and could be activated by suitable treatment (i.e., the use of adjuvant or the coupling of the Ab2 to a carrier). The induction of an allotype-restricted idiotype in mice expressing the wrong allotype (i.e., in mice expressing an allotype which is not associated with the expression of this idiotype) has been observed with suitably manipulated animals (44,49); these restricted idiotypes were found to be part of the silent repertoire of the nonexpressor strains. In another case, a rabbit idiotype has been induced in mice not normally expressing that idiotype (19).…”

Idiotypic Games within the Immune Network

“…Is it possible to orient the repertoire towards a predetermined goal? This was the rationale behind our development of the idiotypic cascade (Cazenave 1977, Urbain et al, 1977, Wikler et al, 1979, Bona et al, 1981, Bluestone et al, 1981, Pene et al, 1983, Sharpe et al, 1984, Uytehaag & Osterhaus 1985, We start with a randomly chosen idiotype Abl (for example, a restricted anticarbohydrate antibody), A similar idiotype has been detected in only 1 out of 60 rabbits immunized in the same way, A second series of rabbits is injected with Abl in order to induce classical antiidiotypic antibodies (Ab2), These purified Ab2 are injected into a third series of rabbits, which produces anti-antiidiotypic antibodies (Ab3), Antigen is then given to the rabbits producing Ab3 antibodies. The resulting antibodies are called Abl', Ab4 antibodies can be induced by immunization with Ab3, In nearly all cases, Abl' antibodies are strongly idiotypically similar to Abl, Rabbit Y is now making the idiotype of rabbit X (for review, see Wikler & Urbain 1984), In most experiments, only a small part of Ab3 binds antigen (see below).…”

Strain-specific silencing of a predominant antidextran clonotype family.

“…Environmental modulation of the genetically encoded repertoire in the form of tolerance (21,(28)(29)(30)(31) and T cell or antibody-mediated idiotypic network effects (6,10,(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) may significantly alter the expression of certain specificities, and thereby participate in the establishment of the primary B cell repertoire. Thus, assessing the relative contribution of genetically encoded vs. environmental influences on the differential expression of predominant clonotype families among various murine strains is essential for an understanding of the establishment of the functional mature B cell repertoire.…”