Germinal center

Germinal centers (or germinal centres; GC) are sites within lymph nodes or lymph nodules in peripheral lymph tissues where intense mature B lymphocytes, otherwise known as centroblasts, rapidly proliferate, differentiate, mutate through somatic hypermutation, and class switch during antibody responses. Once centroblasts have stopped proliferating, they are known as centrocytes. Germinal centres are an important part of the B-cell humoral immune response. They develop dynamically after the activation of B-cells by T-dependent antigen. Histologically, the GCs describe microscopically distinguishable parts in lymphoid tissues.

Process
1. Activated B-cells migrate from the primary focus into the primary follicles follicular system and begin monoclonal expansion in the environment of follicular dendritic cells (FDC).

2. After several days of expansion the B cells mutate their antibody-encoding DNA and thus generate a diversity of clones in the germinal centre. This involves pseudo-random substitutions biased towards regions encoding the antigen recognition surface in a process known as somatic hypermutation.

3. Upon some unidentified stimulus from the FDC, the maturing B cells (Centroblasts) migrate from the dark zone to the light zone and start to expose their antibody to their surface and in this stage are referred to as Centrocytes. The Centrocytes are in a state of activated apoptosis and compete for survival signals from FDCs that present the antigen. This rescue process is believed to be dependent on the affinity of the antibody to the antigen.

4. The functional B-cells have then to interact with helper T cells to get final differentiation signals. This also involves isotype switching for example from IgM to IgG. The interaction with T cells is believed to prevent the generation of autoreactive antibodies.

5. The B cells become either a plasma cell spreading antibodies or a memory B cell that will be activated in subsequent contacts with the same antigen. They may also restart the whole process of proliferation, mutation and selection according to the recycling hypothesis.

The above process involves TNF-alpha.

Morphology at different stages
The morphology of GCs is very specific and shows properties which are characteristic for different stages of the reaction.
 * In an early state of the reaction a network of FDCs is fully filled with proliferating B cells.
 * Later at day 4 of the reaction GCs show a separation of two zones, the dark and the light zone. The former still contains dominantly proliferating cells while the latter one is the area of B cells selection.
 * These zones dissolve after 10 days of GC development which ends after about 3 weeks.

Medical relevance
As germinal centres are important structures of the adaptive immune system, their deregulation is implied in many immune diseases, for example rheumatoid arthritis and many lymphomas.