Antigen receptors, their immunomodulation and the immunoglobulin genes of cattle and swine

Abstract

Abstract The humoral immune system of homeothermic vertebrates represents one of the evolutionary pinnacles of the self/non-self recognition property of life. A specific humoral immune response progresses through three phases; recognition, processing and effector response. ‘Immunomodulators’ can intercede in any or all phases. The term ‘immunomodulation’ has a second meaning in animal science. Namely, the experimental induction of primarily humoral immune responses to hormones, growth factors and other self antigens with the intention of modulating primarily endocrine function. Both of these familiar uses of the term immunomodulation depend on an important property of the humoral immune system: the B cell antigen receptor and its secreted molecular counterpart, the ‘specific antibody’. This review is about antigen recognition and thus concerns: (a) the genetics and structure of the antibody binding site; (b) the ontogeny of B cells and the generation of their repertoire; and (c) the diversity of antibodies among homeotheric vertebrates with special emphasis on the immunoglobulins and immunoglobulin genes of cattle and swine. Although antigen recognition is a B cell function, regulation of their activity during certain phases of the humoral immune response, is the property of T cells and T cell products e.g., lymphokines. While their role is acknowledged, a detailed treatment of their role in the process is outside the scope of this review. The immunoglobulins and immunoglobulin genes of animals show considerable diversity in the development of their antibody repertoire and isotypic variants. Various combinations of combinatorial joining, gene conversion and somatic hypermutation generate the repertoire. Similarly, the effector arm is diverse; rabbits have a single Cγ gene but 13 Cα genes, whereas swine have only one Cα but as many as eight Cγ genes. Moreover, with the exception of closely related species, e.g., rats/mice or sheep/cattle, the effector function of a subisotype designated, e.g., IgG1 in one species, need not be the same as the subisotype designated IgG1 in another as speciation preceded subclass evolution. Determining the biological function of IgG subclasses in farm animals is a fertile area of research. The generation and expansion of the antibody repertoire in farm animals may be a prime target for the first type of immunomodulation described above, as some aspects of repertoire development appear naturally modulated by intestinal flora and maternal factors. Isotype and subisotype selection may be regulated by these same factors which act through complicated cellular pathways involving various lymphokines, cytokines and nuclear transactivating factors. A real need exists to understand antibody repertoire development in farm animals, as the human and mouse may utilize other mechanisms making extrapolation of repertoire development in mice to farm animals dangerous. The magnitude of the diversity in both repertoire development and subisotype constitution and function among animals suggest that the best model for a particular species' immune system is the species itself. This difference also emphasizes the need for standardization of nomenclature and reagents. Finally, a less often discussed example of immunomodulation of economic significance to the livestock industry is discussed. This involves the production of transgenic livestock to produce antibodies for human immunotherapy.