Antibody response inHeterodontus

Abstract

Appropriately selected phylogenetic models are capable of providing insight into genetic mechanisms which may have become obscured during the passage of evolutionary time. In higher vertebrates a complex multigenic family encodes immunoglobulin-variable regions. The mechanisms involved in the expansion of the gene family and the stable maintenance of large numbers of individual genes presently are not understood. By defining the nature of antibody diversity in lower vertebrate species, it may be possible to approach such issues at a more fundamental level. Analyses of the immunoglobulins in Heterodontus francisci (horned shark), a representative phylogenetically primitive elasmobranch, indicate that this species may represent a useful developmental model.

Immunoglobulin VH gene structure and diversity in Heterodontus, a phylogenetically primitive shark.

“…It has been suggested that germline responses predominate in poikilothermic vertebrates, since slower cell cycle rates and pressure for expression of pathogen-specific antibody during ex utero ontogenetic development would make somatic mutation-selection temporally inefficient (33). The immune response characteristics of Heterodontus and another elasmobranch are consistent with this hypothesis as there is no apparent change in antibody fine specificity (11)(12)(13) and affinity (11)(12)(13)34) over prolonged periods of immunization.…”

“…T which inversely complements the gene sequence of a Heterodontus heavy chain constant region peptide, Trp-Lys-LysGly-Glu-Glu (11), and a 24-mer,…”

“…Nati. Acad Sci USA 82 (1985) acid sequencing studies of individual and pooled Heterodontus immunoglobulin VH regions demonstrated the presence of a single residue at each of the first 27 NH2-terminal positions, suggesting that the FR1 segment of the VH gene family was not diversified (11). In the course of these studies, a sequence was determined for a peptide, CN5, corresponding to positions 34-48 spanning the CDR1 and FR2 regions.…”

“…Our present understanding of the evolution of immunoglobulin VH diversity is based on both inter-and intraspecies comparisons of mouse, human (2-7), and reptilian (8)(9)(10) genes. Although inducible humoral immunity has been established in all representative vertebrate species, the elasmobranchs occupy the earliest level of evolutionary development in which immunoglobulins resembling mammalian antibodies have been unequivocally demonstrated (11). Heterodontus francisci, the earliest elasmobranch species studied to date, apparently lacks a heavy chain class shift mechanism and elicits hapten-specific antibody responses that lack interindividual variation and fail to undergo affinity maturation (12,13).…”

Evolution of Antigen Binding Receptors

“…Specifically, upon secondary antigenic challenge, horned sharks do not show a dramatic rise in levels of antibody. Rather, the increase requires repeated monthly immunizations and occurs over a much longer time interval than is seen in mammals (108,109).…”