As we discussed earlier in this chapter, an individual is capable of making a tremendous number of structurally distinct antibodies, perhaps more than 1011, each with a distinct specificity. The ability of antibodies in any individual to specifically bind a large number of different antigens is a reflection of antibody diversity, and the total collection of antibodies with different specificities represents the antibody repertoire. The genetic mechanisms that generate such a large antibody repertoire occur exclusively in lymphocytes. This diversity is generated by random recombination of a limited set of inherited germline DNA sequences to form functional genes that encode the V regions of heavy and light chains as well as by the addition of nucleotide sequences during the recombination process. These mechanisms are discussed in detail in Chapter 8. The millions of resulting variations in structure are concentrated in the hypervariable regions of both heavy and light chains and thereby determine specificity for antigens.

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