Generation of Antibody Diversity

Sequence Shuffling/Changes - The human genome simply does not have enough room to encode a separate gene for each of the millions of different immunoglobulin molecules occurring in B stem cells. Instead, the following two special processes occur in these cells.

> 1. Recombination of Exons - The major source of antibody diversity is recombination of exons. The genomes of higher vertebrates contain "libraries" of exons corresponding to different portions of the immunoglobulin molecule and mechanisms for rearranging these exons to create different combinations in both the heavy and light chains. Shuffling of these exons occurs in B cells and creates new immunoglobulins in individual cells. The details and mechanism of this process are described here.

> 2. Somatic Mutations - An additional source of antibody diversity is somatic mutations (non-germline mutations). In the cells that generate antibodies, certain portions of the variable regions in the immunoglobulin genes mutate at an unusually high rate. The reason for these localized high rates of mutation is still obscure, but this process, together with recombination of gene fragments, can account for the generation of an immense diversity of immunoglobulin molecules. About 100 million combinations can theoretically be made from the library of immunoglobulin gene fragments available in the human genome.

See also: Mechanisms of Protein Mutation, Antibody Structure, Clonal Selection Theory, Gene Rearrangements (from Chapter 25), Generating Antibody Diversity (from Chapter 25)

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