IMMUNOGLOBULIN GENE DIVERSIFICATION BY GENE CONVERSION

This chapter discusses recent advances in the study of gene conversion, primarily in the chicken, and on current models for the molecular mechanism of this form of somatic gene conversion. Most of the higher vertebrates, including teleost fish, the amphibian Xenopus, the reptile Caiman, and most of the mammalian species studied, appear to rely on these combinatorial and junctional mechanisms to generate the primary antibody repertoire. Gene conversion in the chicken immunoglobulin light chain (IgL) locus has been shown to be restricted to the rearranged V gene segment, and does not occur in the leader region, the J gene segment, or within a germline IgL allele that has not undergone V-J joining. The chicken immunoglobulin heavy chain IgH and IgL loci are novel in that, they each contain only single V and J gene segments that are capable of undergoing V(D)J joining in B cell progenitors. In addition, V(D)J recombination in the chicken is not an ongoing development process. V(D)J joining is complete by day 18 of embryogenesis, and chicken progenitor B cells then migrate to a specialized lymphoid organ, the bursa of Fabricius, which is a posterior invagination of the cloaca of avian species. More recently, gene conversion has also been demonstrated to generate somatic immunoglobulin diversity in rabbit, a mammalian species well known for the diversity of its immune response. Although less is known about the mechanism of gene conversion than that of V(D)J joining, recent work has begun to shed some light on the molecular mechanisms involved in immunoglobulin gene conversion. © 1993, Academic Press Inc.