B Cell Activation Flashcards
What are anergic B cells
B cells that have downregulated their bcrs because they recognised soluble ag in bone marrow negative selection
What happens to naive B cells after recognising ag
Clonally expand, proliferate and differentiation into plasma cells releasing antibodies or memory cells
Where is ag looked for by B cells
In B cell area of lymph node
What are the major roles of antibodies
Naturalisation of toxins/pathogens by binding
Opsonisation direct and indirect via fc receptors
Complement activation then Mac
How does opsonisation work
Antibodies with attached pathogen easily bound to phagocytic cells via fc receptors recognising antibody fc domain
Also happens via c3b
How many signals needed to activate B cells to differentiate and proliferate in the lymph node
Atleast 2
Which bcr are they when they leave bone marrow
Igm or igd depending on alternative splicing
Already undergone nhej recombination of vdj
Attached to iga and igb
What is signal 1 and role of iga and igb in this
Binding of ag to bcr
Iga and igb itam domains get phosphorylated and this causes strong b signal
What attaches to ag to cause a stronger bcr signal 1
Complement molecules like c3d
What do complement molecules attached to ag for stronger signal 1 binding to (augment the signal)
Co receptors on B cells (CR2) which can bind eg c3d same time ag binds to bcr
What are the 2 types of ag
Thymus independent ti
Thymus dependant (need T cells)
When can ag provide both signals
If it binds to bcr and something else on B cell surface Eg TI 1 antigens
What other than bcr can TI1 ag bind to to form both signal
Bind to prr like TLR4 via their lps
Allows the proliferation and differentiation of B cells
How are TI 2 ag different to ti 1
TI 2 only recognised by bcr, but by MANY because of their repeated epitopes eg polysaccharides
Cross link many Bcrs at once
Which type of response is not developed in children under 5
Response to TI 2 cross linking antigens (can’t fight pathogens with these)
Is ti2 signal stronger than augmented signal 1 via cr2 bcr complexes
Yes
Why is recognition and signalling via ti2 longer
More ag is needed for cross linking bcr to produce signal 2
Why do TI ag not produce any other antibodies but igm and igd
No class switching occurs (need T cells)
Explain thymus dependant antigen process to signal 2
Signal 1 is the ag binding to the bcr B cell takes it up via rme Processed in endocytic pathway Shown on MHC II to CD4 T cells T cells cause B cell signal 2, aswell as allow class switching
What causes signal 2 to be received in B cells via TD antigen system
T cells activated can express cd40L binding to cd40 on B cells and release cytokines
Both cause signal 2
How does B cell allow T cell activation for the T cell to then activate B cell via cytokines
B cell provides signal 1 and 2 via bcr and cd40 (co stimulatory)
Why are td antigens better for B cell activation
Because ultimately leads to shm and class switching due to cytokine release of T cells
This causes higher affinity B cells and different types (Ti antigens only produce igm)
Why do TD antigens need 2 parts
1 part needs to be recognised by bcr and the other (peptide part) needs to be recognised by tcr on MHC II
How do conjugate vaccines work to deliver antibodies which class switch via TD antigens
TD antigens can be made by attaching proteins (for tcr recognition) to a polysaccharide ag (usually a ti 2). This produces a TD antigen response with T cells and therefore class switching
Why are conjugate vaccines given to children under 5
Because they don’t respond to TI2 antigens like polysaccharides. By attaching a protein they can go through a TD response and release antibodies for the pathogen with ti 2 ag
When cd40 on B cells bind cd40 L in TD antigen response what happens
Signal induced AID for somatic hypermutation
And also class switching
Why are cytokines released from T cells important for B cells
Proliferation / B cell expansion
Also determine type of switching occurs from aid which was induced by cd40 signal
What is b and T cell interaction in the lymph node called
B/t cell conjugates
Where do B cells proliferate and undergo shm after b/t cell conjugates (due to cd40 and cytokines)
Germinal centre of B cell follicles in lymph nodes
What are B cells which are undergoing proliferation, shm and isotype switching called
Centroblasts
When centroblasts stop dividing what are they called
Centrocytes
What is the importance of B cell shm in the germinal centre (aided by cd40 signalling)
Hope to find a better affinity bcr for the ag
Which apc is present in germinal centre with ag presentation ready to be taken off the highest affinity cell to receive a survival signal
Follicular dendritic cells
What does the highest affinity B cell which has taken ag off the fdc do next
Presents to tfh cells
What cytokine causes tfh effector cell production
Il 6 (released by T cells aswell as apc in signal 3)
Why is tfh favoured in germinal centre over other T cells
Ag is presented quicker to these cells to b cells for bcr checking
What happens to outcompeted cells or cells which don’t efficiently bind ag with affinity to tfh
Apoptosis or goes back to germinal centre dark zone for further shm and proliferation
What happens if successful with tfh cell presentation
They become plasma and release antibody or become memory cells
Other than pick the best centrocyte what do tfh help
Release cytokines which cause specific class switches
How do FDC have ag bound to them for presentation to centrocytes
Via their fc receptors and complement receptors
What does CD40 signal prevent in B cells
Apoptosis.
Instead aid is induced and causes class switching and shm in germinal centre
What would cd40L deficiency on T cells cause
Lack of class switching via cd40 interaction lack
Only igm produced
How does cytokine specifically choose what class switch occurs via cd40 activated AID
Breaks dna close to the c region wanted
Eg il 4 breaks up to c e causing igE switch
Can position of ag affect class switch
Yes Eg if ag was in mucosal area iga would be class switched to
