IMMUNOLOGY - Roitt I. - Mir 2000

Chapter 8. Generation of Diversity in Antigen-Recognition Structures

DIVERSITY OF IMMUNOGLOBULINS IN OTHER VERTEBRATES

Shark IMMUNOGLOBULINS have a limited Specificity repertoire

The expansion of the antibody specificity repertoire was critical in vertebrate evolution, and was achieved through different pathways in various animal groups. For example, in elasmobranchs, which include sharks and rays, The Diversity of heavy-chain genes is generated in much the same way as that of λ-type light chains in mice. The basic unit Vн-Dн1-Dн2-Jн-Cн is repeated multiple times in The Genome of these fish; however, with the exception of rearrangements within each such unit, all forms of free recombination between different Gene segments are absent. This leads to a substantial restriction of the antibody specificity repertoire.

The extremely limited Ig gene repertoire of the chicken is expanded by Gene Conversion

Unlike sharks, chickens have an extremely limited number of immunoglobulin-coding genes. For light chains, there is only a single V, J, and C segment, and heavy-chain coding also involves just a single V and J segment. Although about 16 Dн segments have been identified in this species, they are all very similar in nucleotide sequence and contribute little to antibody diversity. Despite such severe constraints, chickens are capable of mounting an Immune Response to a very broad spectrum of Antigens and synthesizing Antibodies with diverse Amino acid sequences.

Upstream of the functional Vl gene lies a DNA region containing 25 nucleotide sequences resembling Vl, but lacking the leader exon, promoters, and the heptamer-spacer-nonamer sequences characteristic of and required for V–J recombination. These pseudogenes are not silent; they participate in gene conversion, a process in which pseudogene fragments are inserted into the functional Vl gene. This process occurs continuously as numerous conversion events throughout the lifespan of the B Cell, even after it leaves the bursa of Fabricius.

A similar mechanism of repertoire expansion operates in the heavy-chain gene locus, which contains up to 100 Vн pseudogenes that participate in conversion.

Gene conversion may serve as a mechanism for expanding the antibody specificity repertoire in rabbits

Rabbit immunoglobulins have long been an enigma, particularly regarding the mechanism regulating the expression of their allotypes. Rabbits possess a fairly large number of Vн genes, yet in more than 80% of B Cells, only a single Vн gene—the one located closest to the D segment—is utilized. As recently established, gene conversion may act as a source of diversity based on this single gene in rabbits.

Pseudogenes may contribute to enhanced antibody diversity in humans

Some V and J segments of human Ig genes are also pseudogenes. However, the potential role of gene conversion in generating rearranged V genes remains a subject of hypothesis and ongoing research.

Antibody diversity in sheep and cattle is generated by somatic Mutations

In ruminants, a single family of Vн genes is expressed throughout life, yet high diversity is achieved through intensive somatic mutagenesis.