Clonal regulation in the response to phosphorylcholine. II. Heterogeneity among T15 idiotype-positive antibodies in inbred and wild mice.

Inbred stains of mice routinely respond to phosphorylcholine (PC)-containing antigens, S. pneumoniae and PC-keyhole limpet hemocyanin, with the production of three major families of antibodies. Two of these groups, the M511 and M603 idiotype (Id) families, are clearly heterogeneous, whereas the third, T15, normally exhibits much less heterogeneity and appears to be monoclonal in many strains. We report here on the occurrence of additional T15 Id+ antibodies which can be detected readily by isoelectric focusing. These antibodies have been observed in 9 of 12 strains examined at an average frequency of 10%. They occur in both the IgG1 and IgG3 isotypes. Collectively, the antibodies comprise a heterogeneous group although cofocusing antibodies were observed in individuals of a strain or between strains. Two H-2-congenic strains, BALB.B and BALB.G, regularly displayed multiple cofocusing T15 Id+ antibodies in each individual. Idiotypic analysis of these antibodies in all strains showed that each contained H, L and H-L-specific variable region determinants common to T15. A surprising finding was the consistent expression of a heterogeneous T15 Id response in two wild Mus musculus lines. Most of these antibodies cofocused with T15 Id+ antibodies in BALB.G or C3H as well as contained strain-specific idiotypic determinants found among inbred mice. These data demonstrate that BALB/c and other inbred strains possess the genetic potential to generate a family of closely related T15 Id+ antibodies. The results further suggest that the restricted response usually seen among inbred strains is not normal and exists because of a highly selective regulatory system.