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Clonal Expansion Theory

By Levi Clancy for Student Reader on

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The discovery of B cells led to a modern theory of antibody production called Clonal Expansion Theory (sometimes still referred to as Clonal Selection Theory). In Clonal Expansion Theory, B and T cells are created with random antibodies, then screened for self-reactivity. When antigen enters the system, it eventually binds to any B cell displaying an antibody specific to that antigen. This binding event triggers the following three steps:

  1. Each activated B cell reproduces, to create an expanding population of identical B cell clones. This population is called a clone.

  2. Some members of the clone become plasma cells. Plasma cells produce and secrete copies of the antibody displayed on the B cell surface.

  3. Other members of the clone are stored as memory cells. Thus, there is a large population of cells to create a strong response when the antigen enters the system again.

Clonal Expansion Theory explains:

  1. Specificity, since only antigen-reactive clones are triggered and only antigen-specific antibody is produced. Diversity is not explained but incorporated into this theory.

  2. Memory, since clonal expansion explains why subsequent responses to an antigen are exponentially stronger than the initial response.

  3. Tolerance, since B and T cells with potential self-reactivity are destroyed or rendered anergic (unable to respond).

Generation of Diversity

An enormous number of specific antibodies and T cells must be generated to respond to the enormous and changing antigenic universe. Immunoglobulin (for B cells) and TCR (for T cells) genes have multiple and similar methods for creating diverse antigenic receptors:

  1. Multiple genes encode different protein sequences with different specificities.

  2. Multiple segments of genes differentially combine to create increased specificities.

  3. Differential junctions following gene segment recombination yield different amino acid sequences.

  4. Somatic (after clonal expansion has begun) mutation of receptor genes in various clones causes changes in germline sequences.