121.18 Somatic recombination also produces variation in the heavy chain of the immunoglobulin molecule.

particular type of heavy ch36ain (I Figure 21.18c-e). Thus, many different types of light and heavy chains are possible.

Somatic recombination is brought about by RAG1 and RAG2 proteins, which generate double-strand breaks at specific nucleotide sequences called recombination signal sequences that flank the V, D, J, and C gene segments. DNA repair proteins then process and join the ends of particular segments together (I Figure 21.19).

In addition to somatic recombination, other mechanisms add to antibody diversity. First, each type of light chain can potentially combine with each type of heavy chain to make a functional immunoglobulin molecule, increasing the amount of possible variation in antibodies. Second, the recombination process that joins V, J, D, and C gene segments in the developing B cell is imprecise, and a few random nucleotides are frequently lost or gained at the junctions of the recombining segments. This junctional diversity greatly enhances variation among antibodies. Third, a high rate of mutation, called somatic hypermutation (the cause of which is unknown), is characteristic of the immunoglobulin genes.

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