Immunoglobulin sequence diversity

Figure 33.7. Immunoglobulin Sequence Diversity. A plot of sequence variability as a function of position along the sequence of the amino-terminal immunglobulin domain of the H chain of human IgG molecules. Three regions (in red) show remarkably high levels of variability. These hypervariable regions correspond to three loops in the immunoglobulin domain structure. [After R. A. Goldsby, T. J. Kindt, and B. A. Osborne, Kuby Immunology, 4th ed. (W. H. Freeman and Company, 2000), p. 91.]...

An impressive example of the kind of permanent changes that can occur in the genome of specialized cells is provided by the genes of immunoglobulins and T-cell receptors. B lymphocytes make tens of millions of antibodies of differing sequence, and T lymphocytes make a similar number of different T-cell receptors. This diversity is established in major part in the DNA but also by alternative splicing and editing of RNA. 

Corbett, S.J., Tomlinson, I.M., Sonnhammer, E.L.L., Buck, D., Winter, G. (1997). Sequence of the human immunoglobulin diversity (D) segment locus a systematic analysis provides no evidence for the use of DIR segments, inverted D segments, minor D segments or D-D recombination. J. Mol. Biol. 270, 587-597. 

Gough, N.M. Bernard, O. (1981). Sequences of the joining region genes for immunoglobulin heavy chains and their role in generation of antibody diversity. Proc. Natl. Acad. Sci. USA 78,509-513. 

Hinds-Frey, K.R., Nishikata, H., Litman, R.T., Litman, G.W. (1993). Somatic variation precedes extensive diversification of germline sequences and combinatorial joining in the evolution of immunoglobulin heavy chain diversity. J. Exp. Med. 178, 815-824. 

Sakano, H., Kurosawa, Y., Weigert, M., Tonegawa, S. (1981). Identification and nucleotide sequence of a diversity DNA segment (D) of immunoglobulin heavy-chain genes. Nature 290, 562-565. 

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