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Chapter: Genetics and Molecular Biology: Generating Genetic Diversity: Antibodies

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Number of Different Antibodies Produced

How many antibodies with different specificities can be generated by a single mouse or human?

The Number of Different Antibodies Produced

How many antibodies with different specificities can be generated by a single mouse or human? If the number is small, then all the information for their synthesis could be explicitly stored in the genome, however unwise this would be, but if it is very large, some other mechanism must be used for generation of the diversity. A straightforward physical measurement made with mice provides an estimation of the lower limit in the number of different antibodies animals are capable of synthesiz-ing.

After injection of mice with phosphocholine linked to a macromole-cule, antibodies are induced. Isoelectric focusing shows that the serum then contains more than 100 different antibodies capable of binding phosphocholine. Each of these has a somewhat different binding speci-ficity. Furthermore, the levels of each of these 100 antibodies have been increased by at least a factor of 100 compared to their level before injection. Together these induced phosphocholine-binding antibodies constitute about 1/200 of the total antibody protein in the serum of the mice.

These numbers lead to the estimate that mice can synthesize antibod-ies with more than 2 × 106 different specificities. The reasoning is as follows. Let N be the number of different antibodies present in a mouse. If these are all synthesized in nearly the same levels, each constitutes about 1/N of the total antibody protein in the serum. If one particular antibody is induced by a factor of 100, that one then constitutes 100/N of the total serum. The 100 different induced phosphocholine-specific antibodies then constitute 100 × (100/N) of the total antibody protein in the serum, which is about 1/200 of the total. That is, 100 × (100/N) = 1/200, or N = 2 × 106. If the mechanisms of antibody synthesis required one gene for each different antibody specificity, these numbers would necessitate that a sizable portion of the genome be used to code for the immune system,




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