A Billion Antibodies -- Understanding the Immune System, Including Autoimmune Thyroid Conditions -- a comprehensive online guide to understanding the immune system, its anatomy, disorders, and other key information

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A Billion Antibodies Understanding the Immune System
Adapted by Mary Shomon Scientists were long puzzled by the opulence of the immune system's resources. The body apparently could recognize and mount unique responses to an endless variety of antigens-but how in the world could all that information be crammed into a limited number of genes? The answer came as a surprise. A typical gene consists of a fixed segment of DNA, which directs the manufacture of a given protein molecule such as insulin. Antibody genes, in contrast, are assembled from bits and pieces of DNAscattered widely throughout the genetic materials. As the B cell matures, it rearranges or shuffles these gene components, picking and choosing among hundreds of DNA segments-some for each of the antibody's variable (V), diversity (D), joining (J), and constant (C) regions. Intervening segments of DNA are cut out; the selected pieces are spliced together. The new gene-and the antibody it encodes-are virtually unique. When the B cell containing this uniquely rearranged set of gene segments proliferates, all its descendants will make this unique antibody. Then, as the cells continue to multiply, numerous mutants arise; these allow for the natural selection of antibodies that provide better and better "fits" for the target antigen. The result of this entire process is that a limited number of genetically distinct B cells can respond to a seemingly unlimited range of antigens.

A similar mechanism was found to control a comparable structure of the T cell, the T cell's antigen receptor. The variable regions of T cell antigen receptors, like those of antibodies, are encoded by V, D, and J segments originally far apart, but which are brought together and fused into a single gene. With numerous candidates for each segment, the number of possible combinations becomes astronomical. However, in contrast to antibody genes, T cell receptor genes do not mutate as the T cells proliferate. This ensures that the self-tolerance imposed in the thymus will not be overthrown by the inadvertent generation of mutant T cell receptors that are anti-self.

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