Page 521 - Veterinary Immunology, 10th Edition

Although random recombination of two or three genes generates
VetBooks.ir much V-region diversity, additional mechanisms can increase this

diversity still further. For example, endonucleases can remove
nucleotides randomly from the cut ends of the genes. As a result,

the precise nucleotide at which V and J genes join varies, leading to
changes in the nucleotide sequence at the splice site and variations
in the amino acid sequence in the V region.

Base Insertion

In immunoglobulin heavy chain gene processing, additional
nucleotides may also be inserted at the V-D and D-J splice sites.
Some of these nucleotides (N-nucleotides) are added randomly by
an enzyme called terminal deoxynucleotidyltransferase (TdT). Up

to 10 N-nucleotides may be inserted between V and D and between
D and J.
Although the random selection of genes from two or three pools

generates a huge number of combinations, not all of these
combinations produce usable antibodies. Some combinations may
generate sequences that cannot be translated into protein. These are
called nonproductive rearrangements. For example, nucleotides are
read as triplets called codons, each of which codes for a specific

amino acid. If the codons are to be read correctly, then the sequence
must be in the correct reading frame. If nucleotides are inserted or
deleted so that the codon reading frame is changed, the resulting

gene may code for a totally different amino acid sequence. If this
“frameshift” results in inappropriate splicing, translation is
prematurely terminated.
It is probable that nonproductive rearrangements are produced in
two out of three attempts during B cell development. When this

happens, the B cell has several additional opportunities to produce
a functional antibody. For example, immature B cells initially
rearrange one of the IGK genes (Fig. 17.8). If this fails to produce a

functional light chain, they switch to the other IGK allele for a
second attempt. If this does not work, the B cell will use one of the
IGL alleles, and if this fails, the second IGL allele represents the last
resort. If all these efforts fail to produce a functional light chain, the
B cell cannot make a functional immunoglobulin. It will undergo

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