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:
- Each activated B cell reproduces, to create an expanding population of identical B cell clones. This population is called a clone.
- Some members of the clone become plasma cells. Plasma cells produce and secrete copies of the antibody displayed on the B cell surface.
- 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:
- Specificity, since only antigen-reactive clones are triggered and only antigen-specific antibody is produced. Diversity is not explained but incorporated into this theory.
- Memory, since clonal expansion explains why subsequent responses to an antigen are exponentially stronger than the initial response.
- 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:
- Multiple genes encode different protein sequences with different specificities.
- Multiple segments of genes differentially combine to create increased specificities.
- Differential junctions following gene segment recombination yield different amino acid sequences.
- Somatic (after clonal expansion has begun) mutation of receptor genes in various clones causes changes in germline sequences.