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Concept
Clonal selection
Summary
In immunology, clonal selection theory explains the functions of cells of the immune system (lymphocytes) in response to specific antigens invading the body. The concept was introduced by Australian doctor Frank Macfarlane Burnet in 1957, in an attempt to explain the great diversity of antibodies formed during initiation of the immune response. The theory has become the widely accepted model for how the human immune system responds to infection and how certain types of B and T lymphocytes are selected for destruction of specific antigens.
The theory states that in a pre-existing group of lymphocytes (both B and T cells
), a specific antigen activates (i.e. selects) only its counter-specific cell, which then induces that particular cell to multiply, producing identical clones for antibody production. This activation occurs in secondary lymphoid organs such as the spleen and the lymph nodes. In short, the theory is an explanation of the mechanism for the generation of diversity of antibody specificity. The first experimental evidence came in 1958, when Gustav Nossal and Joshua Lederberg showed that one B cell always produces only one antibody. The idea turned out to be the foundation of molecular immunology, especially in adaptive immunity.
The clonal selection theory can be summarised with the following four tenets:
Each lymphocyte bears a single type of receptor with a unique specificity (generated by V(D)J recombination).
Receptor occupation is required for cell activation.
The differentiated effector cells derived from an activated lymphocyte bear receptors of identical specificity as the parent cell.
Those lymphocytes bearing receptors for self molecules (i.e., endogenous antigens produced within the body) are destroyed at an early stage.
In 1900, Paul Ehrlich proposed the so-called "side chain theory" of antibody production. According to it, certain cells exhibit on their surface different "side chains" (i.e. membrane-bound antibodies) able to react with different antigens. When an antigen is present, it binds to a matching side chain.
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