Page 517 - Veterinary Immunology, 10th Edition

VetBooks.ir Generation of Junctional Diversity

Gene Rearrangement

The most obvious way to generate V-region diversity is to select
one V gene at random from the available pool and join it to one
randomly selected J gene; a process called recombination. Since

many V and J genes are available, the number of possible
combinations can be very large. For example, if there are 100 V
genes and 10 J genes, then 100 × 10 = 1000 different V regions can be
constructed.
Light chain assembly requires the combination of one V, one J,

and one C gene. During B cell development, the intervening genes
must first be removed, and discarded. The first step in this process
is to identify the sites where the DNA has to be cut. Thus V and J

genes have sites called switch regions at each end that guide the
process (Fig. 17.4). Cutting is the function of an “activation-
induced” cytidine deaminase (AID). When a B cell receives the
appropriate signals telling it to eliminate unwanted genes, AID
deaminates the cytidines in the specific switch regions involved

(Fig. 17.5). As a result, these cytidines are converted to uracils. This
conversion results in DNA “damage” and, as a result, both strands
of the DNA are cut by an endonuclease at these points. The looped-

out genes are chopped off, and the free ends of the DNA are
“rejoined” by a DNA ligase so that the V and J genes form a
continuous sequence. Two sets of enzymes are used in this process.
Endonucleases cut the DNA at two points, thus excising unwanted
genes. Following this, DNA ligases join the free ends to form a

continuous sequence.

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