MOLECULAR CHARACTERIZATION OF MONOCLONAL CRI(A)-POSITIVE ANTI-ARSONATE ANTIBODIES DERIVED FROM IDIOTYPE-NEGATIVE MICE BEARING A LIGHT-CHAINPOLYMORPHISM

We have elicited anti-arsonate antibodies bearing the major cross-reac tive idiotype (CRI(A)) in a double congenic idiotype-negative strain ( C.C58.AL-20) bearing a light chain polymorphism that has previously be en shown serologically not to complement idiotype-positive heavy chain s. Using the idiotype cascade (Ab1 --> Ab2 --> Ab3 --> --> Ab1'), CRI( A)-positive antibodies were raised and monoclonal antibodies were isol ated and characterized serologically and by nucleotide sequence analys is. Two types of idiotype-positive anti-arsonate antibodies were gener ated in the C.C58.AL-20 strain. One group of hybridomas used the canon ical V(H)1.8 heavy chain gene segment with V(kappa)10 variant light ch ains. A second group used a V(H)GAM3.8 heavy chain with V(kappa)10 var iant light chains. This latter heavy-light pairing has been observed i n CRI(A)-like responses previously in BALB/c mice after idiotypic mani pulation (or rarely after antigen alone). These studies demonstrate th e plasticity of the immune response when manipulated with idiotype rea gents as well as its structural variability. Additionally, they provid e important insights into the potentials of idiotype vaccines.