Isogeneic monoclonal antibodies against anti‐α(1 → 3)dextran idiotypes II. Neonatally induced idiotope‐specific suppression: a comparative analysis

Abstract

From a panel of isogeneic monoclonal anti-idiotope antibodies several were used as agents in neonatal idiotope suppression. They differed from one another in isotype, and in idiotope specificity, as described in the preceding report (Eur. J. Immunol. 1987. 17: 255). In their effects they were compared with respect to the following variables: minimum dose required for suppression; duration of suppression, and its relationship to the dose applied neonatally; half-life of anti-idiotope in the immune system of the young mice; specificity of suppression as achieved by a given anti-idiotope: in how far does it affect idiotopes defined by alternate anti-idiotopes? The following results were obtained: the minimum effective dose varied widely between anti-idiotopes. One, belonging to the IgM class, was completely ineffective; others varied from approximately 10 micrograms/mouse, required for complete suppression, to approximately 100 micrograms/mouse. The dose-response characteristic was independent of whether the state of suppression was tested (by immunization against alpha(1----3)dextran) 26 days or 70 days after neonatal anti-idiotope treatment. We take this as an indication that the anti-idiotope effect occurs during an early postnatal period. There appeared to be a relationship between the rate of decay of anti-idiotope in the system and the dose required for complete suppression: the faster the decay, the more is needed initially. The persistence of effective molecules in the animals appears to depend on their isotype (as has been noted by others before): IgM decays fastest, and was ineffective in our experiments; IgG1 stays longest, and the smallest dose was required for suppression. IgG2b was intermediate. The specificity of neonatal suppression was clearly correlated with the serological specificity of the anti-idiotope monoclonal antibodies, as well as with the representation of the corresponding idiotopes in physiological anti-dextran sera, as described in the preceding report: private anti-idiotopes suppressed their counterpart idiotopes only, while the public anti-idiotope suppressed all other idiotopes in concert.

Stimulation of the Same B‐Cell Population by Thymus‐Independent Dextran and by Thymus‐Dependent Oligosaccharide‐Carrier

“…More sensitive indicators of variable parts of antibodies are idiotopes [36,38], The cross-reacting idiotype Id-X of the Dex-specific response is never found in Igh haplotype b mice [39], and is not expressed on BALB/c antibodies carrying the K light chain [8]. We used the panel of eight idiotope-specific monoclonal antibodies (Hid-1 to Hid-8), which define idiotopes (Id 1 to Id-8) on MI04E, and which are also found in the immune response to Dex of BALB/c , but not of C57BI/6 [19,23]. The analysis of antisera raised by immunization with the TD antigens N4-and N7-CSA showed that all eight idiotopes were present and that they constituted about the same proportions of the Dex binding antibodies as in Dex raised sera, although the individual variations were larger.…”

“…ELISA. Unless otherwise stated, all antisera were tested on Dexcoated plates [19]. The myeloma protein M104E (anti-Dex, IgM/A) served as the reference standard for tbe quantitation of /i-or A carrying antibodies.…”

“…Idiotope determinations were done with ELISA plates coated with the corresponding monoclonal anti-M104E-idiotope antibody (Hid) at the concentration of 1 ^g/well [19]. The secondary antibody was Lsl36-POD [19].…”

“…The idiotype (Id) of Dex-specific antibodies, raised by Dex immunization of BALB/c mice, has been well characterized by a set of eight different monoclonal antibodies, directed against idiotopes on M104E molecules (Hid 1-8) [19,23]. Some Ids, like Id-1 or Id-7, as defined by Hid-1 and Hid-7, respectively, are found in the Dex-specific sera of every mouse and in about one to one relation with Dex reactivity; they are thus called public idiotopes.…”