Scientists long wondered how all the genetic information needed to make millions of different antibodies could fit in a limited number of genes.
The answer is that antibody genes are spliced together from widely scattered bits of DNA located in two different chromosomes. Each antibody molecule is made up of two separate chains, a heavy chain and a light chain. The heavy chain is where the binding of antigens occurs, so much genetic variation is involved in its assembly. For example, to form a heavy chain, 1 of 400 possible variable gene segments (V) combines with 1 out of 15 diversity segments (D) and 1 out of 4 joining (J) segments. This makes 24,000 possible combinations for the DNA encoding the heavy chain alone. As this part of the gene assembles, it joins the variable coding segments with those for the constant-C segments of the heavy-chain molecule.