RESTRICTED VH GENE USAGE AND GENERATION OF ANTIBODY DIVERSITY IN RABBIT

The presence of V(H)a allotypic specificities on nearly all rabbit Ig molecules has perplexed immunologists for many years. How could these allotypic specificities be inherited as if controlled by alleles if the germline has hundreds of V(H)a allotype-encoding genes and if most of these genes are used in VDJ gene rearrangements. I review recent data indicating that the allelic inheritance of the V(H)a allotypes can be explained by preferential utilization of the D-proximal V(H) gene V(H)1 in VDJ gene rearrangements. The preferential usage of one V(H) gene, however, limits the contribution of combinatorial joining of multiple V(H), D and J(H) gene segments to the generation of antibody diversity. The roles of somatic gene conversion and somatic mutation in generating antibody diversity are discussed. Further, the limited usage of germline V(H) genes in normal, allotype-suppressed and the mutant Alicia rabbit as well as the molecular basis of latent allotypes and V(H)/C(H) recombinants is reviewed.