Germinal centre
Image labeled in German, but "Keimzentrum" visible in upper right.
Gray's	subject #175 689

Germinal centres (GC) are sites within lymph nodes or lymph nodules in peripheral lymph tissues where intense mature B lymphocytes, otherwise known as Centrocytes rapidly proliferate, differentiate, mutate through somatic hypermutation and class switch during antibody responses. 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.

Contents 1 Process 2 Morphology at different stages 3 Medical relevance 4 References 5 See also 6 External links

[edit] 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 random substitutions, deletions and insertions due to 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.^[1]

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.^[2]

[edit] 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.^[3] 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.

[edit] 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^[4] and many lymphomas.

[edit] References

1. ^ Thorbecke GJ, Amin AR, Tsiagbe VK (1994). "Biology of germinal centers in lymphoid tissue". FASEB 8: 832–840. PMID 8070632. 
2. ^ http://medicineworld.org/cancer/lead/1-2008/drugs-used-to-treat-rheumatoid-arthritis.html
3. ^ Meyer-Hermann ME (2002). "A Mathematical Model for the Germinal Center Morphology and Affinity Maturation". J. theor. Biol. 216: 273–300. doi:10.1006/jtbi.2002.2550. PMID 12183119. 
4. ^ http://medicineworld.org/cancer/lead/1-2008/drugs-used-to-treat-rheumatoid-arthritis.html

[edit] See also

• Lymph node

[edit] External links

• UIUC Histology Subject 563
• Histology at BU 07103loa - "Lymphoid Tissues and Organs: lymph node, germinal center"
• Hyperlinked Human Histology
• Summary of lecture on B-cell development with Q'n'A collection
• MedEd at Loyola Histo/practical/lymph/hp12-42.html
• Overview at okstate.edu

v • d • e Immune system: Lymphatic system (Lymph, Lymphocytes, Lymph vessels) (TA A13.1-2, GA 8) Primary Bone marrow · Thymus (Hassall's corpuscles) Secondary Spleen (process blood) structural: Hilum · Trabeculae Red pulp (Cords of Billroth, Marginal zone) White pulp (Periarteriolar lymphoid sheaths, Germinal center) blood flow: Trabecular arteries · Trabecular veins Lymph nodes (process extracellular fluid) lymph flow: Afferent lymph vessels · Cortical sinuses · Medullary sinuses · Efferent lymph vessels T cells: High endothelial venules B cells: Primary follicle/Germinal center · Mantle zone · Marginal zone layers: Capsule/Trabeculae · Subcapsular sinus · Cortex · Paracortex · Medulla (Medullary cord) · Hilum MALT (process mucosa) GALT · Peyer's patches · Germinal center lymphatic organ navs: anat, physio, lymphatic disease/splenic disease/thymus disorders/thymus neoplasia/vascular tumors, proc