Page 525 - Veterinary Immunology, 10th Edition

VetBooks.ir Box 17.1

Methods of Generating Antibody

Diversity

VJ and VDJ gene recombination

Base deletion

Base insertion

Somatic mutation

Combinatorial association

Gene conversion

Receptor editing

Following initial exposure to an antigen, B cells proliferate and

undergo antigen-driven selection in the dark zones of germinal
centers (Chapter 12). The mutations in immunoglobulin V genes are
generated by the same enzymes used for class switch
recombination. They are triggered by antigen cross-linking of two
BCRs, by the binding of CD40 to CD154, and by the binding of

CD80 to CD28. These signals activate cytidine deaminase (AID),
which deaminates the cytidines in V gene DNA and converts them
to uracils. These uracils are recognized as errors (after all, uracil is

not normally found in DNA), and their appearance therefore
triggers repair processes. Other enzymes delete the uracils and
leave a gap that is repaired by DNA polymerases using randomly
selected nucleotides. The gaps are “patched” by short nucleotide
sequences. As a result of this “repair,” V gene sequences gradually

change as the B cells respond to antigens. On average, one amino
acid changes each time a B cell divides (see Fig. 17.5).
The degree to which a B cell responds to antigen is directly
related to the strength (affinity) with which its receptors bind that

antigen. The better the fit between antigen and receptor, the greater
will be the stimulus received by the B cell. If a BCR cannot bind an

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