Germination center

Lymph nodes with two secondary follicles: (1) capsule, (2 ) marginal sinus , (3) germinal center (secondary follicle), (4) parafollicular space, (5) trabecula

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The germinal center is the name given to the reactive changes that occur inside a lymph follicle after contact with the antigen , which turns it into a secondary follicle . The germinal center is a topographical separation of different developmental stages of B cells that is visible under a light microscope and that arises due to immunological processes. The dark inner zone contains proliferating activated B cells ( centroblasts ). These migrate as centrocytes into the outer light zone and are selected at its edge. This is followed by a mantle and marginal zone. The B memory cells develop in the latter .

The germinal centers are also known as "risk zones" since many lymphomas are derived from B lymphocytes.

Immunological processes before germinal center formation

If B cells bind a native, soluble peptide antigen with their B cell receptors , the receptors and their bound antigens are absorbed into the cell. The antigens are cleaved proteolytically and bound to MHCII molecules as peptide fragments of 13 to 17 amino acids . These MHCII-peptide complexes are presented on the cell membrane.

These B cells then reach the T cell areas of secondary lymphatic organs . There may be already activated T cells specific for the same antigen . With their T-cell receptors, these recognize the MHCII-peptide complexes presented by the B cells. They hold the B cells in place, activate them and with them form a primary focus in the T cell zone in which the B cells proliferate.

Some of the offspring of these B cells form extrafollicular foci two to three days after activation (e.g. in the red pulp of the spleen or in the medullary cords of the lymph nodes ), in which they proliferate and differentiate into plasma cells . They secrete IgM and IgG with low antigen affinity in the foci. Most are short-lived and have a 50% survival rate of three to five days. The foci will disappear after about 14 days.

The other part of the B cells migrates together with the T cells by which they were activated to the B cell follicles, where they form germination centers at the border to the T cell zone.

Development of a germinal center

When a germinal center develops - the germinal center reaction - a dark zone first arises in which the activated B cells ( centroblasts ) are subject to massive clonal expansion. A class change of the constant region of the heavy chain can take place and somatic mutations can be inserted into the genes for the variable regions of the light and heavy chains of the immunoglobulins . This can lead to an increase or decrease in the affinity of the B cell receptors for their antigen.

The B cells then migrate out of the dark zone into the network of follicular dendritic cells and form the outer, light zone of the germinal center. The impression of a “bright zone” in the histological picture arises from the fact that the B cells give rise to large basophilic B immunoblasts that migrate from the edge to the center.

The B cells ( centrocytes ) no longer divide. The follicular dendritic cells present immune complexes consisting of complement , antibodies and antigens, which they have bound via Fc and complement receptors. If the centrocytes' receptor affinity for the antigen is too low, their receptors cannot bind to the antigen presented. If their affinity is high enough, however, they can bind and involve these antigens, break them down and express the peptide fragments, bound to MHCII, on the cell surface.

The centrocytes then migrate to the edge of the bright zone of the germinal center, where they meet the CD4 T cells, which are also clonally multiplied to a certain extent and to which they present the MHCII-peptide complexes. This is where a selection takes place: The B cells that have gained a lower affinity and do not present any antigen to the T cells receive no survival signal - they die apoptotically . Only B cells with a high enough affinity for the original antigen that have taken up antigens and present them to the T cells receive survival signals.

They either develop into plasma cells or into memory cells . The development into plasma cells takes place via the plasmablast stage. Plasmablasts are still able to divide, but can already secrete antibodies. Plasma cells also secrete antibodies, but are no longer able to divide. The development into memory B cells takes place in the marginal zone. You can also return to the dark zone of the germinal center and undergo a germinal center reaction again. Most of the plasma cells that develop in germinal centers migrate to the bone marrow , where they secrete antibodies of the IgG , IgE and IgA classes with high affinity for the antigen . They are also long-lived (sometimes longer than a year).

During the entire process of the germinal center formation, the B cells circulating through the B-cell follicles are pushed more and more outwards and form a mantle zone surrounding the germinal center.

literature

• Charles Janeway , Paul Travers, Mark Walport, Mark Shlomchik: Immunology. 5th edition, Spektrum Akademischer Verlag, Heidelberg 2002, ISBN 3-8274-1079-7 ; Online version in English , 5th edition, 2001.

Individual evidence

1. ↑ Johannes W. Rohen, Elke Lütjen-Drecoll: Functional Histology . Schattauer Verlag, 4th edition 2000, ISBN 978-3-7945-2044-2 , p. 188.