Combinatorial VJ and VDJ Joining Generates Diversity

The contribution of multiple germ-line gene segments to antibody diversity is magnified by the random rearrangement of these segments in somatic cells. It is possible to calculate how much diversity can be achieved by gene rearrangments (Table 5-2). In humans, the ability of any of the 51 VH gene segments to combine with any of the 27 DH segments and any of the 6 JH segments allows a considerable amount of heavy-chain gene diversity to be generated (51 X 27 X 6 = 8262 possible combinations). Similarly, 40 VK gene segments randomly combining with 5 JK segments has the potential of generating 200 possible combinations at the k locus, while 30 VX and 4 JX gene segments allow up to 120 possible combinations at the human X locus. It is important to realize that these are minimal calculations of potential diversity. Junc-tional flexibility and P- and N-nucleotide addition, as mentioned above, and, especially, somatic hypermutation, which will be described shortly, together make an enormous contribution to antibody diversity. Although it is not possible to make an exact calculation of their contribution, most workers in this field agree that they raise the potential for antibody combining-site diversity in humans to well over 1010. This does not mean that, at any given time, a single individual has a repertoire of 1010 different antibody combining sites. These very large numbers describe the set of possible variations, of which any individual carries a subset that is smaller by several orders of magnitude.

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Essentials of Human Physiology

Essentials of Human Physiology

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  • nile
    How to calculate number of rearrangments needed to create specific antibody?
    7 years ago

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