The clonal selection theory is a hypothesis which states that individual B-cell lymphocytes express a receptor that is antigen-specific. This would be determined before the antibody ever encounters the antigen. Activation occurs within the lymph nodes, spleen, or similar lymphoid organs, which then encourages cloning, so that each individual cell is able to target an individual antigen with effectiveness.
It can be summarized through these four key points.
- Every lymphocyte offers a single receptor that has an individualized unique specificity.
- For cell activation to occur, receptor occupation is required.
- Every differentiated effector cell that has been derived from a lymphocyte which has been activated will bear a receptor that is identical in specificity as its parent cell.
- Lymphocytes that bear receptors for self-molecules are going to be deleted, primarily at an early stage.
This theory of antibody product was first proposed in 1957 by Dr. Frank Burnet, an Australian doctor who was attempting to explain how a diverse array of antibody was able to be produced during an immune response. Experimental evidence of this theory came just a year later when Joshua Lederberg and Gustav Nossal were able to show that one B-cell always produces a single antibody.
History of the Clonal Selection Theory
Paul Ehrlich is credited with proposing a side-chain theory of antibody production, which essentially stated that certain membrane-bound antibodies were able to react to different antigens. The antigen would bind to the matching “side-chain,” which would then create duplication so that the entire antigen could be removed throughout the body.
Although it would prove to be somewhat inaccurate, when it was first proposed in 1900, it was much closer to what evidence would show to be true than other theories regarding immunology at the time.
Then, in 1955, Niels Jerne offered the idea that soluble antibodies are actually present before any infection actually takes place. This Danish immunologist suggested that the body would select the correct type of antibody in response to the antigen.
Burnet essentially combined these two ideas together to formulate his hypothesis, which would become backed by empirical evidence.
Who Is Sir Frank Macfarlane Burnet?
Born in September 1899, Frank Burnet was the son of a Scottish emigrant to Australia. Due to his family structure, he often found himself alone as a child, so his pursuits were often “bookish” in nature. This led to an emphasis in studying that would benefit him later on in life.
Dr. Burnet would win the Nobel Prize in 1965 for predicting acquired immune tolerance. His development of the clonal selection theory is his best known work.
He earned his Doctorate of Medicine in 1924 from the University of Melbourne and then his PhD from the University of London in 1928. Much of his work, including the development of the clonal selection theory of antibody production, took place at the Walter and Eliza Hall Institute of Medical Research that is located in Melboure. Burnet served as the director of the institute from 1944-1965.
Burnet would continue to work at the University of Melbourne after his retirement in 1965 and remained active in his field of study. He was a founding member of the Australian Academy of Science and even served as its president from 1965-1969.
In 1978, Burnet was made a Knight o the Order of Australia and has received numerous honorary doctorates, the Lasker Award, the Royal Medal, and the Copley Medal in addition to the Nobel Prize.
What Are the Results of the Clonal Selection Theory?
Because of the clonal selection theory, Dr. Burnet was able to propose that tissues could be transplanted successfully into a foreign recipient. This has brought about numerous advances into the fields of tissue and organ transplantation, along with an even deeper understanding of what the immune system is able to do.
Immune network theory is also based on the clonal selection theory, which is another hypothesis which would win a Nobel Prize in 1984. Proposed by Niels Kaj Jerne, it proposes that the immune system functions in the style of a network. Variable parts of the lymphocytes and their molecules would be regulated by how they interact with one another.
Much of the understanding that we have today regarding the immune system comes from the work and proposals of Frank Burnet. The clonal selection theory of antibody production has become the foundation of immunology and modern medicine, allowing us to be able to better treat health issues due to the understanding it has provided.