Clonal Selection Theory

Prior to the discovery of the clonal selection model, efforts to understand why such a broad repertoire of antibody specificities occurs were concentrated on notions of ‘instruction’. These hypothesised that antigens served as blueprints for the development of antibodies. Where they fell short was in their inability to provide an explanation for the occurrence of a second immune response or for the development of affinity.

Clonal selection theory is an immunological scientific hypothesis that describes how immune system cells (lymphocytes) respond to certain antigens that invade the body. In 1957, Australian physician Frank Macfarlane Burnet proposed the notion in an effort to explain the wide variety of antibodies generated during the commencement of the immune response.  The idea has gained widespread acceptance as a model for how the body’s immune system reacts to infections and how certain kinds of B and T cells are chosen for antigen-specific destruction According to the theory, rather than causing the forming an antibody special to itself, as some immunologists believed, an antigen entering the body binds to one specific antibody selected from among a vast repertoire of antibodies are produced early in the organism’s life, despite being contentious at the time, this notion eventually established the basis of contemporary immunology.

Clonal selection and immunological memory

As a result of their initial introduction to antigen, plasma cells cease to produce antibodies and eventually die. Memory cells survive in higher numbers than the initial B cells, helping the body to respond more swiftly to the same antigen when it is exposed to it a second time.

After being exposed to an antigen for around one week, the body can produce modest quantities of soluble antibodies. A subsequent exposure to the antigen, on the other hand, results in a significantly quicker reaction and antibody levels that are many orders of magnitude greater. The capacity of the antibody to bind to antigen rises as a result of the secondary reaction as well. Vaccination is based on the memory of the antigen and the stimulation of the immune response.In addition to being quicker, a secondary immune reaction (secondary encounter to an antigen) creates antibodies that have a binding affinity that can be up to 10,000 times more than the initial antibody produced. This increased affinity is due to a process that affects the variable sections of the heavy and light chain of the memory cells through somatic mutations that are exclusive to the memory cells. A random process, it has the potential to increase antigen binding if it happens to be successful.

In the course of two cell divisions, the mechanism produces a mutation. Re-exposure to antigen is more likely to result in the clonal proliferation of memory cells, which are responsible for the production of antibodies with the highest affinity. The mutations that result in enhanced affinities will be clonally chosen by antigen in a manner similar to that of the main immune response. In the absence of T cell signalling, cells that have an inactive antibody will perish as a result of apoptosis.

Theories that have been proven correct by clonal selection

Burnet and Peter Medawar collaborated on the study of immunological tolerance, a phenomenon that can be explained by clonal selection as well as other means. As long as the exposure of cells happens early in the organism’s development, it will be tolerated by the organism and will not cause an immune response to be triggered. There are a large range of lymphocytes seen in the immune system, ranging from cells that accept self tissue to cells that do not tolerate self tissue. Only cells that are tolerant of their own tissue endure the embryonic stage, however. The lymphocytes that form as a result of the introduction of non-self tissue are those that recognise the non-self tissues as belonging to the self.

When Burnet claimed that tissues may be effectively transplanted to foreign recipients under particular conditions in 1959, the world took notice. This research has resulted in a far better knowledge of the immune system, as well as significant advancements in the field of tissue transplantation. In 1960, Burnet and Medawar were jointly awarded the Nobel Prize in Physiology or Medicine.

It was postulated in 1974 by Niels Kaj Jerne, that the immune system is composed of an interconnected network of cells whose activity is governed by interactions between their variable portions and the substances they release. In Immune Network Theory, the idea of clonal selection is a fundamental building block. As a result of his contributions to immunological network theory, Jerne was awarded the Nobel Prize in Physiology or Medicine in 1984 for his work.

Conclusion

As explained in the article, Clonal Selection theory is a process proposed to explain that how the single B or T cell, which recognizes an antigen that enters the human body is selected from pre-existing cell pool of a varied antigen specificities and then altogether reproduced to generate a clonal cell population, which eliminates the antigen.