View source for Germinal center

{{About|lymph primary follicles|ovarian primary follicles|Folliculogenesis}}
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  Caption      = Germinal center of a lymph node showing proliferation and development stages of a B cell . |
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'''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 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 immunity|humoral immune response]]. They develop dynamically after the activation of [[B-cell]]s by T-dependent [[antigen]].
[[Histology|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 cell]]s (FDC).

2. After several days of expansion the B cells mutate their
[[antibody]]-[[encode|encoding]] [[DNA]] and thus generate a diversity of [[Clone (genetics)|clone]]s in the
germinal center. 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 [[Centrocyte]]s. The
Centrocytes are in a state of [[activation|activated]] [[apoptosis]] and compete for
survival signals from FDCs that present the
antigen. This rescue process is believed to be dependent on the [[Affinity (pharmacology)|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.<ref>{{cite journal | author=Thorbecke GJ, Amin AR, Tsiagbe VK| title=Biology of germinal centers in lymphoid tissue| journal=FASEB | volume=8 | year=1994 | pages=832–840 | pmid=8070632 | issue=11}}</ref>

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 [[cell growth|proliferation]], [[mutation]] and [[selection]] according to the
recycling hypothesis.

The above process involves [[TNF-alpha]].<ref>http://medicineworld.org/cancer/lead/1-2008/drugs-used-to-treat-rheumatoid-arthritis.html</ref>

==Morphology at different stages==
The [[morphology (biology)|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.<ref>{{cite journal | author=Meyer-Hermann ME|title=A Mathematical Model for the Germinal Center Morphology and Affinity Maturation |journal=J. Theor. Biol. |volume=216|year=2002|pages=273–300 | pmid=12183119|doi=10.1006/jtbi.2002.2550 | issue=3}}</ref> 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 centers are important structures of the [[adaptive immune system]], their deregulation is implied in many immune diseases, for example [[rheumatoid arthritis]]<ref>http://medicineworld.org/cancer/lead/1-2008/drugs-used-to-treat-rheumatoid-arthritis.html</ref> and many [[lymphomas]].

==See also==
* [[Lymph node]]

==References==
<references/>

==External links==
* {{UIUCHistologySubject|563}}
* {{BUHistology|07103loa}} - "Lymphoid Tissues and Organs: lymph node, germinal center"
*[http://www.bio.davidson.edu/courses/immunology/hyperhuman/Lymphnode/medula/node40_0.html  Hyperlinked Human Histology]
*[http://www.owlnet.rice.edu/~bios423/Lecture%20outlines/BCELLSH.htm Summary of lecture on B-cell development] with Q'n'A collection
* {{LoyolaMedEd|Histo/practical/lymph/hp12-42.html}}
* [http://www.cvm.okstate.edu/instruction/mm_curr/histology/HistologyReference/HRLym.htm Overview at okstate.edu]

{{Lymphatic system}}

[[Category:Lymphatic system]]

[[de:Keimzentrum]]
[[Category:2Fix]]