The Germinal Centre
Author(s): David Dorward, Hannah McManus and Genevieve McMahon
This section will describe the specialised arm of the immune response which is integral in producing an efficient secondary B cell response.
By the end of this CAL you should understand:
- what a germinal centre is
- the importance of a germinal centre to the B cell response
- how the germinal centre is formed
- the interaction of specialised cells within the germinal centre – including the follicular dendritic cell
Introduction Part 1 of 6
When B cells are activated from interaction with their cognate antigen and T cell, they proliferate and differentiate into antibody-secreting plasma cells.
Plasma cells are specific for the antigen and so can help to fight the initial infection, but are not necessarily of very high affinity. Therefore, to make B cells more effective in the fight for survival they enter a secondary phase where they can increase this affinity and create memory. This happens within the germinal centre.
What happens in the germinal centre and how does it work? Part 2 of 6
When a B cell is initially activated by a T cell it does one of two things:
- Becomes activated and forms short-lived plasma cells working locally to help the immune response
- Moves into the germinal centre and differentiates further into –
- Long-lived plasma cells – these sit in the bone marrow and secrete antibody, keeping your levels high even once the infection has gone
- B memory cells – these sit and wait for the next infection to arrive, and create a massive response if it does
Germinal centres allow memory B cell formation, plasma cell formation, immunoglobulin class switching and leads to the selection of B cells of higher affinity for their cognate antigen (known as affinity maturation).
Germinal centres are formed within B cell follicles, and can be divided into two groups:
- Primary follicle – a follicle containing B cells
- Secondary follicle – a follicle containing a germinal centre
Germinal Centre Formation Part 3 of 6
It takes only 2-4 ‘founder B cells’ to initiate a germinal centre. These have been activated previously by helper T cells.
Founder B cells divide very rapidly to create lots of progeny. Within 5 days they can create a large germinal centre.
Like the lymph node, the germinal centre can also be split into zones. B cells go through 2 stages of development when maturing in the germinal centre, becoming centroblasts and centrocytes, and this defines the different zones:
So what is this selection process? Part 4 of 6
To understand this we need to describe the follicular dendritic cell, (FDC). These aren’t actually dendritic cells but look similar.
FDCs have a special property in that they can stick antigen-antibody complexes to themselves, helping the B cells in the germinal centre increase in affinity. To survive the germinal centre, a differentiating B cell needs to interact with its antigen to get the signals it needs to survive.
However, all the antigen attached to FDCs in the germinal centre is already bound to antibody from the first batch of early plasma cells which differentiated after T cell activation. Therefore, to get a survival signal and bind to the antigen, the maturing B cell needs to have a BCR (and therefore antibody) of higher affinity, in order to displace the pre-existing antibody.
This means that the B cells that survive the germinal centre are those that have a BCR or antibody of highest affinity to the antigen, and therefore are more effective in the immune response.
How do these FDCs aquire the antibody:antigen complexes? Part 5 of 6
FDC acquisition of antigen-antibody complexes also involves B cells of the germinal centre.
B cells within the germinal centre pick up antibody-antigen complexes from macrophages outside of the B follicle and transport them to FDCs within the germinal centre. This means that antibody-antigen complexes specific to any current infection are taken into germinal centres to permit a strong response to be created against it.
The point of the germinal centre is not only to increase the affinity of existing cells but also to create a long lasting protection against infection, in the form of memory.
To do this, B cells also need the help of a helper T cell – the T follicular helper cell, – to fully differentiate into either a plasma or memory cell.
This is done by the centrocyte acquiring an antigen complex from the FDCs in the germinal centre and carrying it to the periphery of the follicle, where it interacts with a corresponding T follicular helper cell. The two interact and dual activation occurs – the centrocyte differentiates into a plasma or memory cell (depending on expression or repression of certain transcription factors) and the helper T cell is itself activated.
Conclusion Part 6 of 6
If centrocytes that fail to achieve terminal differentiation into a plasma cell die through apoptosis. Natural selection in the germinal centre is brutal.