A private idiotype can become recurrent through genetic recombination and gene(s) unlinked to the Igh locus governs...

Any immune response is characterized by its idiotypic profile. Two different kinds of idiotype (Id) have been described. Private Id are restricted to a few individuals from a species while recurrent Id appear in a large majority of individuals from the same species immunized with the same antigen. We describe, in this report, an experimental model whereby a private Id can become recurrent through genetic recombination. The immune response of A mice against the hapten arsonate is characterized by a recurrent Id called cross-reactive idiotype A (CRIA). A strongly CRI, called CRIA-like, can be occasionally detected in some BALB/c mice (5% to 10%) immunized with arsonate. Molecular studies show that CRIA and CRIA-like antibodies have highly homologous D segments and identical light chains. By contrast, their VH segments are vastly dissimilar. We have examined the anti-arsonate response of inbred strains of mice whose Igh loci are recombinant between those of A/He and BALB/c. Interestingly, we have observed that the CRIA-like Id which is private in BALB/c becomes recurrent in the AXC-1 strain which harbors the VH genes from BALB/c, the DH and CH genes from A/He. Structural studies demonstrate that highly homologous, VH, VL and D segments are used in BALB/c and AXC-1 mice. The basis for this differential expression of highly similar genes could be linked to the DH locus. However, F1 mice stemming from the cross between AXC-1 and BALB/c do not express the Id. The backcross analysis shows that the non-expression of the Id in F1 mice depends on genes unlinked to the Igh locus.