The genetic control of antibody formation.
Abstract: Studies of the molecular biology of lymphoid cells have markedly increased our understanding of how millions of different antibodies can be synthesized by a single animal. To date, the most detailed understanding has been achieved for the mouse, primarily because of the relatively greater experimental availability of this species. These studies, as well as those involving other species, have shown that the complete genes for antibody polypeptide chains are assembled from disparate genetic elements which are originally widely separated in the genome. The assembly process itself, together with the coding information present in the germ line genetic elements, contributes to the diversity of structure (and thus combining specificities) shown by mature antibody molecules. Specifically, the diversity of structure characteristic of antibody variable regions is due to three distinct mechanisms: innate variability of germ line genes; mismatching of individual gene segments during their somatic rearrangement leading to junctional diversity; and somatic mutation in variable region genetic material during or after the rearrangement. These processes lead to the wide array of combining specificities that permit the humoral immune system of a mature animal to interact with essentially any non-self antigen which it encounters. Complex genetic rearrangements are also responsible for the class switching phenomenon long known to be characteristic of the humoral immune response. A form of homologous recombination between constant region genes, possibly mediated by specific "switching" enzymes, is now believed to be involved in this phenomenon. It is also currently believed that the restriction of gene rearrangement processes to one of the two possible chromosomes of a diploid pair in each cell is responsible for the phenomenon of allelic exclusion that has long been associated with the normal functioning of mammalian B-cells.
Publication Date: 1983-03-01 PubMed ID: 6408785DOI: 10.1016/0165-2427(83)90055-7Google Scholar: Lookup
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The research paper discusses how the genetic control of antibody formation in mouse lymphoid cells leads to a diverse structure of antibodies. The authors suggest this diversity is created by several mechanisms, including recombination and mutation of genes, which allow these cells to combat a variety of foreign antigens. They also propose that gene rearrangements and the phenomenon of allelic exclusion contribute to this versatility.
Genetic Control of Antibody Formation
- The paper describes the profound understanding gained in our knowledge of antibody formation due to the study of the molecular biology of lymphoid cells in mice.
- The researchers report that antibody genes are constructed from different genetic elements that are originally scattered throughout the genome.
- This assembly process, along with the coding information within these genetic elements, shapes the diversified structure of mature antibodies.
Mechanisms Contributing to Diversity
- The study highlights three main mechanisms underlying the unique variability in the structure of antibodies’ variable regions: innate variability of germ line genes, junctional diversity due to mismatching of individual gene segments during somatic rearrangement, and somatic mutation in variable region genes during or post-rearrangement.
- These processes yield a broad array of combining specificities, allowing the humoral immune system to counter virtually any foreign antigen it comes across.
Genetic Rearrangements and Class Switching
- Complex genetic rearrangements are also indicated to be behind the “class switching” phenomenon, a characteristic feature of the humoral immune response.
- The researchers speculate that a form of homologous recombination between constant region genes, potentially facilitated by “switching” enzymes, plays a role in class switching.
Phenomenon of Allelic Exclusion
- The paper also posits that the restriction of gene rearrangement processes to one chromosome of a diploid pair in each cell leads to the phenomenon of allelic exclusion, a well-known aspect of normal B-cell function in mammals.
- This restriction ensures that each B-cell produces antibodies of only a single specificity, thereby promoting immune system diversity.
Cite This Article
APA
Seide RK, Kehoe JM.
(1983).
The genetic control of antibody formation.
Vet Immunol Immunopathol, 4(1-2), 3-42.
https://doi.org/10.1016/0165-2427(83)90055-7 Publication
Researcher Affiliations
MeSH Terms
- Alleles
- Animals
- Antibody Diversity
- Antibody-Producing Cells / immunology
- B-Lymphocytes / immunology
- Cats
- Dogs
- Horses
- Humans
- Immunoglobulin Constant Regions / genetics
- Immunoglobulin Variable Region / genetics
- Immunoglobulin lambda-Chains / genetics
- Immunoglobulins / biosynthesis
- Immunoglobulins / genetics
- Mice
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