The primary antibody response in BALB/c mice to the T-independent bacterial antigen dextran B1355S [alpha(1 leads to 3)dextran] (Dex) was studied by means of isoelectric focusing, hemagglutination and immunodiffusion techniques. In response to a single immunization with 10 micrograms Dex all mice produce specific IgM antibodies. In addition, about 30% of conventionally raised BALB/c and BALB/c nu/ + mice, but 95% of germ-free (GF)-raised normal BALB/c and 100% of athymic BALB/c nu/nu mice produce specific IgG class anti-Dex antibodies. These antibodies include all IgG subclasses, carry predominantly the lambda light chain and the cross-reactive J558 idiotype and are specific for the alpha(1 leads to 3)glucosidic linkage. As compared to athymic and GF-raised mice, conventionally raised mice exhibit only a weak IgG response. The pronounced IgG production of GF-raised mice was not altered when adult mice were removed from their GF environment and housed under conventional conditions for several weeks prior to immunization with Dex. Reconstitution with isolated splenic T cells from conventionally raised, unprimed BALB/c mice reduces the remarkable capacity of BALB/c nu/nu mice to produce IgG anti-Dex antibodies. These findings suggest that the reduced capacity of conventionally raised BALB/c mice to mount an IgG response to the T-independent antigen Dex is due to a T cell-mediated suppressive mechanism which is neonatally induced by contact with environmental, i.e. bacterial, antigens.

BALB/c and BALB/c nu/nu mice were shown to express to a variable extent in their response against dextran B1355S (Dex), an idiotype which is present on the Dex-reactive BALB/c myeloma protein MOPC 104E. Injection of minute amounts of syngeneic anti-MOPC 104E idiotype antisera into neonatal euthymic or athymic BALB/c mice suppressed this idiotype in the Dex-specific response of the adult animals. When spleen cells from suppressed BALB/c mice were transferred into irradiated BALB Ighb mice the state of suppression persisted. Data are discussed with respect to possible mechanisms regulating expression of this idiotype.

A new congenic mouse strain (C57BL/6-Igh-Vb-Ca) with a recombinant chromosome 12 is described. It carries the Igh-1a allele, but shows the serological characteristics of C57BL/6 when analyzed for idiotype expression with respect to the antigens dextran and (4-hydroxy-5-iodo-3-nitrophenyl)acetyl (NIP). We analyzed liver DNA from one animal for restriction fragment length polymorphism by hybridization to probes detecting members of nine VH gene families and DH segments, and compared it to DNA from animals carrying the nonrecombinant haplotypes Igha and Ighb, respectively. The breakpoint of recombination maps to the region carrying members of VH gene families VGAM3.8, PC7183 and Q52. The CB8KN strain which according to the serological analysis carries a recombinant Igh locus (Igh-Va-Cb) on BALB/c background was also analyzed. In this strain the breakpoint of recombination again maps to the region carrying members of VH gene families VGAM3.8, PC7183 and Q52. Our results show that the VH genes of families PC7183 and Q52 are interspersed and map to the region next to the DH locus. At least one gene from the VGAM3.8 family also maps to this region in the Igha and the Ighb haplotype.

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.

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