Generation of Antibody Diversity

As the organization of the immunoglobulin genes was deciphered, the sources of the vast diversity in the variable region began to emerge. The germ-line theory, mentioned earlier, argued that the entire variable-region repertoire is encoded in the germ line of the organism and is transmitted from parent to offspring through the germ cells (egg and sperm). The somatic-variation theory held that the germ line contains a limited number of variable genes, which are diversified in the somatic cells by mutational or recombinational events during development of the immune system. With the cloning and sequencing of the immunoglobulin genes, both models were partly vindicated.

To date, seven means of antibody diversification have been identified in mice and humans:

■ Multiple germ-line gene segments

■ Junctional flexibility

■ P-region nucleotide addition (P-addition)

■ N-region nucleotide addition (N-addition)

■ Somatic hypermutation

■ Combinatorial association of light and heavy chains

Although the exact contribution of each of these avenues of diversification to total antibody diversity is not known, they each contribute significantly to the immense number of distinct antibodies that the mammalian immune system is capable of generating.

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  • Daryl Dickson
    What are the seven means of antibody diversification?
    8 years ago

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