Studies of Idiotypic Antibodies

Serum or urine from normal adult Lewis rats can be shown to contain detectable amounts of idiotypic, antigen-binding receptors with specificity for the major histocompatibility complex locus antigens of the rat, the Ag-B locus antigens. Such purified naturally occurring receptor molecules, be they of T- or B-lymphocyte origin, can be used in a polymerized form to provoke the production of auto-anti-idiotypic antibodies when injected back into normal Lewis rats. As a consequence of this autoimmunity, lymphocytes of these Lewis rats can be shown to be depleted of cells carrying the relevant idiotypic receptors signifying reactivity against a given Ag-B locus-determined antigen(s). This specific lack of idiotypic lymphocytes is manifested as a selective loss of reactivity against the relevant Ag-B-incompatible antigens as measured by graft versus host or MLC reactions. Furthermore, autoimmune Lewis rats display specific transplantation tolerance against the skin grafts from the relevant strain, as demonstrated by specific prolongation of graft survival. A further indication of the specific tolerence state of these rats comes from the highly reduced ability to produce circulating antibodies against the relevant Ag-B antigens. No side effects of these autoimmunization procedures have been noted so far. It would thus seem clear that a prolonged state of specific transplantation tolerance can be achieved via autoimmunization against the individual's naturally occurring idiotypic, antigen-binding receptors.

Section: Mixed Leukocyte Cultures (Mlc)mentioning

confidence: 99%

mentioning

confidence: 99%

Specific transplantation tolerance induced by autoimmunization against the individual's own, naturally occurring idiotypic, antigen-binding receptors.

Binz¹,

Wigzell²

1976

“…Though simultaneous complementary responses were induced intentionally and quite artifically in these experiments, the potential may exist in nature for other antigens and antibodies to stimulate comparable responses. Antibodies or antigen-antibody complexes can induce anti-idiotypic responses, and the inference is that complexes formed in vivo may account for induction of autogenous anti-idiotypic antibodies (22)(23)(24)(25)(26)(27)(28)(29)(30)(31). Also, preliminary studies in our laboratory suggest that some complex antigens may contain complementary determinants, each of which stimulates directly one of the complementary antibody responses (D. A. Rowley, unpublished observations).…”

Section: Discussionmentioning

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.

“…Discussion There is a growing body of evidence that anti-idiotypic antibodies can specifically regulate a number of immunological phenomena such as the suppression (11)(12)(13) or enhancement (14,15) of antibody production and the specific inhibition of graft-vs.-host (16,17) and mixed leukocyte culture reactivity (18). In most instances anti-idiotypic antibodies were raised by allo-(17) or heteroimmunization (14) though the production of autoanti-idiotypic antibodies has also been reported in rabbits (19). The data presented in this paper clearly demonstrate that anti-idiotypic antibodies raised syngeneically in strain 2 and 13 guinea pigs against anti-BPO-BGG can specifically and markedly suppress in vitro lympho- Table I. cyte proliferation of cells from syngeneic guinea pigs.…”

Section: Does the Interaction Of D Strain 2 And D Strain 13 Bpo-bgg Smentioning

confidence: 99%

Histocompatibility antigens and genetic control of the immune response in guinea pigs. III. Specific inhibition of antigen-induced lymphocyte proliferation by strain-specific anti-idiotypic antibodies.

Geczy¹,

Geczy²,

Weck³

1976

The in vitro T-cell proliferation induced by penicilloylated bovine IgG (BPO-BGG) in sensitized strain 2 and strain 13 guinea pigs could be specifically blocked by strain-specific antisera presumably directed against cell membrane-associated immunoglobulin idiotypes. The anti-idiotypic antisera were prepared in strain 2 and strain 13 guinea pigs against immunoadsorbent purified anti-BPO-BGG antibodies which had been raised in strain 2 and strain 13 animals. Strain 13 antistrain 13 anti-BPO-BGG (a strain 13 BPO-BGG) suppressed the in vitro BPO-BGG response of cells from immunized strain 13 animals but did not inhibit the response of cells from immune strain 2 animals. Conversely, the corresponding antiserum raised in a strain 2 combination (a strain 2 BPO-BGG) only inhibited the in vitro BPO-BGG response of strain 2 cells. Furthermore, the inhibitory activity of the antisera could only be absorbed by immune cells from the syngeneic strain. The activity of the a strain 13 BPO-BGG serum was highly specific; the inhibitory activity could only be absorbed by BPO-BGG-sensitive strain 13 cells. The inhibitory activity of the anti-idiotypic sera was predominantly associated with the 19S fraction. The data suggest that immune cells and in particular T lymphocytes from strain 2 and strain 13 guinea pigs possess strain-specific recognition structures from BPO-BGG with the same idiotypes as the corresponding strain-specific immunoglobulins. Furthermore, the production of such inhibitory anti-idiotypic sera was restricted to syngeneic combinations, which suggests a potential role of autoanti-idiotypic antibodies in the regulation of the immune response. The anti-idiotypic antisera used here are apparently directed against gene products not associated with the strain 2 or strain 13 major histocompatibility complex.