Antibody genes have very special structures. It has become clear by
observing antibody genes in germ cells, which do not produce
antibodies, that their structure is very different from various known
genes.
For example, by observing how genes on one light chain are
arranged in DNA it was found that the part called the variable region
is coded separately in several sequences some distance apart in the
DNA. Moreover, it was found that the part that codes the invariable
region has its own DNA sequence separated from the variable region.
On the other hand, if one observes the genes in cells that produce
antibodies, namely B cells or B lymphocytes, in contrast to the case
of germ cells, the DNA used for the variable region exists as one
continuous sequence. In other words, the V and J gene segments are
contiguous (see Fig. 2). Furthermore, in this cell, when the gene is
expressed, RNA is produced using this DNA as a template. Then
recombination occurs during the process in which the RNA moves from
the nucleus to the place where protein is synthesized. By doing so, a
sequence not directly related to protein sequence, called an Intron
(intervening sequence) is eliminated, messenger RNA is produced, and
protein is synthesized on the ribosome (the substance that synthesizes
protein).
Recombination of Antibody Gene Fragments
An important point of this discovery is that, unlike the behavior of
the genes which has been recognized up to the present, in the case of
antibody genes, gene fragments are restructured during the generation
and the development of a cell.
When this phenomenon is investigated in more detail, it is more
complicated in the case of heavy chains. In the case of heavy chains,
instead of two types of gene fragments, the variable region is coded
by three different types, called V, D, and J. In this case, in order
for this gene to be expressed, one of the many Vs, one of the many Ds,
and one of the Js are connected to each other in series. A complete
gene which can produce a heavy chain will be created by this process.
What is the significance of the existence of these genes as fragments
in germ cells? In Fig.3, in the case of a heavy chain, about 300 V
gene fragments, 20 D gene fragments, and 5 J gene fragments exist in
germ cells. In the process when a cell is developed and B lymphocytes
are generated, one of each type of fragment from the pools of these
three gene fragments are selected. A complete gene for a heavy chain
can be created by the various combinations. Therefore, it can be
simply calculated that, from all the combinations of 300 types of V
gene fragments, 20 types of D gene fragments, and 5 types of J gene
fragments, 24,000 different types of variable regions can be created.
As many as 24,000 different types of genes can be produced from very
few, several hundred at most, gene fragments inherited from the
parents. The somatic cell theory was proved by this discovery.