Page 460 - Veterinary Immunology, 10th Edition

VetBooks.ir Germinal Centers

As mentioned above, a key feature of the humoral immune
response is the progressive increase in antibody binding affinity

over time. This process takes place within germinal centers (Fig.
15.19). Thus germinal centers are sites where antigen-driven B cell
proliferation, somatic mutation, and positive and negative selection
of B cell populations occur. Germinal centers are divided into two
zones based on staining patterns, a light zone containing dendritic

cells, some B cells and Tfh cells, and a dark zone that mainly
consists of dividing B cells (see Fig. 12.10). In the early stages of the
reaction, B cells stimulated by antigen and Tfh cells migrate to the

dark zone. There they proliferate and mutate their antibody V
genes. B cells divide every 6 to 8 hours so that within just a few
days a single B cell develops into a clone of several thousand cells.
During this phase of rapid B cell division, the BCR V region genes
mutate randomly, on average once per division. This repeated

mutation generates large numbers of B cells whose BCRs differ
from the parent cell. Once these cells have been clonally expanded,
a process that takes 10 to 20 days, they migrate to the light zone

where they are presented with antigen by the dendritic cells.
Because of their V gene mutations, some of these B cells bind the
antigen with greater affinity, and others bind it less strongly. A
process of selection thus occurs. If a mutation has resulted in
greater affinity for the antigen, this stimulates more B cell

proliferation. Thus cycles of rapid somatic mutation and selection
lead to a rapid improvement in antigen binding—a process called
affinity maturation. These antigen-selected B cells eventually leave

the germinal center to form either plasma cells or memory B cells.
In contrast, those B cells that have reduced antigen binding
undergo apoptosis and are removed by macrophages. Thus the B
cell population that emerges from a germinal center is very
different from the population of cells that entered it. In addition to

somatic mutation of BCR V genes, BCRs also undergo class
switching within germinal centers. The germinal center eventually
dissipates after the B cell response has peaked (Chapter 12).

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