T-B Cell Interactions Flashcards
(30 cards)
Where are B cell follicles?
In the cortex of the lymph nodes
What is the first step of B cell activation?
Naive B cells in follicles bind intact antigens (unprocessed/broken down) via their B cell receptor.
The B cell internalises the antigen, processes it and then present the peptides on MHC II
What is the B cell receptor?
A surface immunoglobulin
What happens once the naive B cell presents the peptide on MHC II?
The previously activated CD4+ T cell migrates to follicle edge (which is the T-B border), where it presents the peptide on MHC II to the T cell’s TCR
What is cognate interaction?
Where the T cell receptor on an activated CD4+ binds to the peptide-MHC II on the B cell. This confirms antigen-specific activation.
Also, CD40 (B cell) binds to CD40L (T cell), which is an essential costimulatory signal
What is the importance of the CD40-CD40L costimulation?
- Promotes antibody class switching
- Supports germinal centre formation
- Drives differentiation into memory B cells
What would happen if the CD40-CD40L binding were not to occur (1. class switching)?
AID would not be activated, so B cells would be stuck producing IgM antibodies only.
Severe deficits in other isotypes (G, A, E) which are essential for immune defense like:
- neutralisation
- mucosal immunity
- anti-parasite defence
- allergic responses
What would happen if the CD40-CD40L binding were not to occur (2. germinal centre formation)?
There would be no productive germinal centre formation, meaning no somatic hypermutation or affinity maturation.
The result would be low-affinity and poorly-protective antibodies.
What would happen if the CD40-CD40L binding were not to occur (3. memory B cells)?
There would be no memory cell differentiation, so no long-term B cell support.
This would result in no long-term immunity and poor response to vaccines
What is a disease linked to CD40-CD40L interaction?
Hyper-IgM syndrome:
Results from a genetic CD40L deficiency, and causes immunodeficiency.
Marked by elevated IgM but severely reduced IgG, IgA and IgE.
Causes recurrent opportunistic infections
What is AID?
AID is the essential enzyme that initiates both somatic hypermutation and class-switching recombination by deaminating cytidine to uracil, triggering DNA breaks in switch regions for CSR and mutations in variable regions for SHM.
What happens once the B cell becomes activated?
Clonal expansion- production of daughter B cells specific to that antigen
Following initial clonal expansion, what are the two possible routes for activated B cells?
- Extrafollicular response
- Germinal centre response
What is the extrafollicular response?
Some activated B cells differentiate quickly into short-lived plasma cells. This occurs outside the follicles in medullary cords.
Produces short lived, lower affinity IgM antibodies
Why are antibodies produced in extrafollicular response shorter-lived and lower affinity?
As they undergo little or no somatic hypermutation
What is the purpose of the extrafollicular response?
Rapid defense mechanism before the high affinity response develops
What is the germinal centre response?
Activated B cells migrate to B cell follicle, and form a germinal centre with help from T follicular helper (Tfh) cells
What are the two zones of the germinal centre?
- Dark zone
- Light zone
What processes occur in the dark zone of the germinal centre?
Site of rapid proliferation (centroblasts) and somatic hypermutation
What processes occur in the light zone of the germinal centre?
Non-dividing site. Selection of high-affinity B cells via interaction with follicular dendritic and Tfh cells
Overall, what 3 processes occur in germinal centre?
Somatic hypermutation
Class-switch recombination
Affinity selection
What are plasma cells and memory B cells?
They are the two possible cells that B cells differentiate into following germinal centre.
What do plasma cells do?
Migrate to bone marrow or mucosal tissue, and secrete large amounts of antibody.
They have the effector role in clearing a current infection
