WordNet

of or belonging to neither the right nor the left politically or intellectually
a building dedicated to a particular activity; "they were raising money to build a new center for research" (同)centre
(American football) the position of the player on the line of scrimmage who puts the ball in play; "it is a centers responsibility to get the football to the quarterback"
a position on a basketball team of the player who participates in the jump that starts the game
the position on a hockey team of the player who participates in the face off at the beginning of the game
a place where some particular activity is concentrated; "they received messages from several centers" (同)centre
the sweet central portion of a piece of candy that is enclosed in chocolate or some other covering (同)centre
the object upon which interest and attention focuses; "his stories made him the center of the party" (同)centre, center of attention, centre of attention
an area that is approximately central within some larger region; "it is in the center of town"; "they ran forward into the heart of the struggle"; "they were in the eye of the storm" (同)centre, middle, heart, eye
a point equidistant from the ends of a line or the extremities of a figure (同)centre, midpoint
a cluster of nerve cells governing a specific bodily process; "in most people the speech center is in the left hemisphere" (同)centre, nerve_center, nerve centre
(football) the person who plays center on the line of scrimmage and snaps the ball to the quarterback; "the center fumbled the handoff" (同)snapper
(basketball) the person who plays center on a basketball team
(ice hockey) the person who plays center on a hockey team
politically moderate persons; centrists
the middle of a military or naval formation; "they had to reinforce the center"
move into the center; "That vase in the picture is not centered" (同)centre
equally distant from the extremes (同)halfway, middle, midway
containing seeds of later development; "seminal ideas of one discipline can influence the growth of another" (同)originative, seminal
a fractional monetary unit of several countries
(American football) putting the ball in play by passing it (between the legs) to a back; "the quarterback fumbled the snap" (同)snap
being or placed in the center

PrepTutorEJDIC

芽の,胚(はい)種の / (発達の)初期段階の;原始の
〈C〉『セント』(1ドルの1/100;米国・カナダの貨幣単位;《略》￠) / 〈C〉1セント銅貨 / 〈U〉(単位としての)100
中軸(中心)を持つ

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/13 12:45:10」(JST)

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This article is about lymph primary follicles. For ovarian primary follicles, see Folliculogenesis.

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.

Process[edit]

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.^[1]

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[edit]

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.^[2] 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[edit]

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

References[edit]

^ 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.

External links[edit]

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

UpToDate Contents

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1. びまん性大細胞型B細胞性リンパ腫の予後 prognosis of diffuse large b cell lymphoma
2. 体液性免疫応答 the humoral immune response
3. 非ホジキンリンパ腫の病理の概要 overview of the pathobiology of the non hodgkin lymphomas
4. IgG4関連疾患の概要 overview of igg4 related disease
5. 成人における末梢リンパ節腫大の評価 evaluation of peripheral lymphadenopathy in adults

English Journal

A8.36 Activated human B cells induce an inflammatory phenotype in synovial fibroblasts.

Tretter T, Stoerch H, Tykocinski L, Moradi B, Lorenz HM.Author information Department Internal Medicine V, Div. Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.AbstractBACKGROUND AND OBJECTIVES: Synovial fibroblasts (SF) are key players in pathogenesis and progression of rheumatoid arthritis (RA). A cross-talk between immune cells and SF is suggested to contribute to chronification of the disease. RA-SF can be found in close proximity to B cells in vivo, with activated proliferating B cells often organised in germinal center- like pseudofollicles. While various reports deal with the influence of SF on B cells, our intention was to clarify the potential influence of B cells on SF MATERIALS AND METHODS: Highly purified CD19(+) B-cells were separated from PBMC by magnetic cell sorting. B-cells were polyclonaly stimulated by BCR-cross-linking with anti-IgM/IgG Antibody or SAC (Staphylococcus aureus Cowan I antigen) and cocultured with SF, that were isolated from synovial biopsies of patients with osteoarthritis (OA-SF). After 48-72h cytokine production was determined by ELISA of cell culture supernatants and phenotypical changes in both cell populations were determined by flow cytometry
Annals of the rheumatic diseases.Ann Rheum Dis.2014 Mar 1;73 Suppl 1:A91. doi: 10.1136/annrheumdis-2013-205124.210.
BACKGROUND AND OBJECTIVES: Synovial fibroblasts (SF) are key players in pathogenesis and progression of rheumatoid arthritis (RA). A cross-talk between immune cells and SF is suggested to contribute to chronification of the disease. RA-SF can be found in close proximity to B cells in vivo, with acti
PMID 24489344

A3.8 Association between clinical, histopathological and molecular features in primary Sjogren's Syndrome: a retrospective study.

Carubbi F, Alunno A, Cipriani P, Di Benedetto P, Ruscitti P, Berardicurti O, Bistoni O, Caterbi S, Bartoloni E, Gerli R, Giacomelli R.Author information Rheumatology Unit, University of L'Aquila, Italy;AbstractBACKGROUND AND OBJECTIVES: Although minor salivary gland (MSG) biopsy is the diagnostic gold standard to identify focal lymphocytic sialoadenitis (FLS) in primary Sjögren's syndrome (pSS), the association between MSG histopathology and clinical picture is still unknown. Histological studies are based on hematoxilin and eosin (H&E) staining, however new approaches such as immunofluorescence or molecular biology assays, allow to stratify pSS patients according to other variables including germinal center (GC)-like structure presence and cytokine expression. Such evaluation may represent a powerful tool to be employed in clinical practice in order to predict pSS clinical picture and eventually disease prognosis. We aimed to investigate the relationship between the characteristic of the immune infiltrate, GCs presence, molecular expression of cytokines involved in inflammation and lymphoneogenesis, laboratory and clinical features in a large cohort of pSS patients.
Annals of the rheumatic diseases.Ann Rheum Dis.2014 Mar 1;73 Suppl 1:A45. doi: 10.1136/annrheumdis-2013-205124.102.
BACKGROUND AND OBJECTIVES: Although minor salivary gland (MSG) biopsy is the diagnostic gold standard to identify focal lymphocytic sialoadenitis (FLS) in primary Sjögren's syndrome (pSS), the association between MSG histopathology and clinical picture is still unknown. Histological studies are bas
PMID 24489224

A3.1 Pathogenic role of IL-17 producing double negative (DN) T cells in primary sjogren's syndrome.

Alunno A, Carubbi F, Bistoni O, Caterbi S, Bartoloni E, Santoboni G, Mirabelli G, Cannarile F, Valentini V, Cipriani P, Giacomelli R, Gerli R.Author information Rheumatology Unit, University of Perugia;AbstractBACKGROUND AND OBJECTIVES: We recently demonstrated that a CD3(+) T cell population, that lacks both CD4 and CD8 molecules, defined as double negative (DN), is expanded in the peripheral blood of patients with long-standing primary Sjögren's syndrome (pSS), produces IL-17, accumulates in minor salivary glands (MSGs) and is resistant to corticosteroids (CS) in vitro. Since IL-17 represents a key cytokine in the pathogenesis of pSS, we aimed to investigate glandular and peripheral DN T cells in early phases of the disease in order to verify a possible correlation with clinical parameters, MSGs histological patterns and possibly ectopic lymphoneogenesis.
Annals of the rheumatic diseases.Ann Rheum Dis.2014 Mar 1;73 Suppl 1:A42. doi: 10.1136/annrheumdis-2013-205124.95.
BACKGROUND AND OBJECTIVES: We recently demonstrated that a CD3(+) T cell population, that lacks both CD4 and CD8 molecules, defined as double negative (DN), is expanded in the peripheral blood of patients with long-standing primary Sjögren's syndrome (pSS), produces IL-17, accumulates in minor sali
PMID 24489217