|Germinal center of a lymph node showing proliferation and development stages of a B cell .|
|Gray's||subject #175 689|
Germinal centers (or germinal centres; GC) are sites within secondary lymphoid organs where mature B lymphocytes proliferate, differentiate, mutate their antibodies (through somatic hypermutation), and switch the class of their antibodies (for example from IgM to IgG) during a normal immune response to an infection.
During this process of rapid division and selection, B cells are known as centroblasts, and once they have stopped proliferating they are known as centrocytes. Germinal centers 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.
1. Activated B-cells migrate from the primary focus of infection into the primary follicles and begin monoclonal expansion in the environment of follicular dendritic cells (FDC). During this time they are referred to as centroblasts.
2. After several days of expansion the B cells undergo somatic hypermutation, a process by which they mutate their antibody-encoding DNA and thus generate a diversity of clones in the germinal center. This involves pseudo-random substitutions biased towards regions encoding the antigen recognition surface of the antibodies the B cells produce. This process is an example of how affinity maturation occurs, whereby greater affinity antibodies are produced and selected for after antigen recognition. During this time they also undergo isotype switching, or class switching.
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 express their antibody on the cell 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, meaning the cells will die unless "rescued" by these survival signals. This rescue process is believed to be dependent on the affinity of the antibody to the antigen. That is, if a B cell has mutated to have an antibody with more affinity to an antigen, it will be more likely to survive. In this way the immune system can better recognize antigens.
4. The functional B-cells then have to interact with helper T cells to get final differentiation signals. This also involves isotype switching, for example from the antibody type IgM to another antibody type such as IgG. The interaction with T cells is believed to prevent the generation of autoreactive antibodies.
5. The B cells become either a plasma cell which are cells which secrete large quantities of antibody or a memory B cell that can be reactivated in subsequent contacts with the same antigen. B cells 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.
- Thorbecke GJ, Amin AR, Tsiagbe VK (1994). "Biology of germinal centres in lymphoid tissue". FASEB 8 (11): 832–840. PMID 8070632.
- Meyer-Hermann ME (2002). "A Mathematical Model for the Germinal Centre Morphology and Affinity Maturation". J. Theor. Biol. 216 (3): 273–300. doi:10.1006/jtbi.2002.2550. PMID 12183119.
- UIUC Histology Subject 563
- BU Histology Learning System: 07103loa - "Lymphoid Tissues and Organs: lymph node, germinal centre"
- Hyperlinked Human Histology
- MedEd at Loyola Histo/practical/lymph/hp12-42.html