Lecture 6 - B cell activation Flashcards
When B cells recognise self Ag they are negatively selected. This could be clonal deletion, receptor editing or making the B cell anergic. Where does negative selection of B cells occur?
Bone marrow.
Where do B cells get activated?
Like T cells, B cells are activated in the secondary lymphoid tissues. They are activated when they encounter non-self Ag.
Like T cells, B cells require signals to be activated. Describe signal 1.
- Signal 1 occurs when Ag binds to BCR. The BCR is associated with Iga and IgB. Signal 1 can be enhanced if Ag has complement attached. If complement is attached to Ag then it can also bind to complement receptor 2 (CD2) on surface of B cell, increasing the signal 1.
Signal 1 of B cell activation can be enhanced if complement is attached to antigen. Ag then binds to CR2. What is the CR2 co receptor complex on BCR?
CD2/CD19/CD81
Describe signal 2 of B cell activation.
Signal 2 depends on thymus dependent (TD) or thymus- independent (TI) antigens.
TD antigens are the best way to activate a B cell. T cells are involved. Firstly, Ag binds to BCR and then B cell processes the Ag and presents it on an MHC class 2 molecule. CD4+ T cell recognises the peptide and activates the B cell.
TI-1 Ag activate B cells by firstly binding to BCR, then binding to TLR on their surface. eg gram negative bacteria bind to TLR4.
TI-2 Ag activate B cell by forming a crosslink with many other antigens which bind to the BCRs. This takes longer.
For thymus independent, as there are no T cells, there is no class switching, therefore antibody released in IgM
TD antigens are much better than TI antigens as they produce a more efficient response and class switching can occur. How are conjugate vaccines made and why are they good?
Conjugate vaccines involve changing TI antigens to TD which increases the efficiency of the vaccine.
This is done by coupling the capsular polysaccharide (which is the TI antigen) to a protein such as Tetnus Toxoid. This is then processed by the B cell and the peptide is displayed on an MHC class 2 molecule, and recognised by CD4+ T helper cells. IgM is produced and then IgG due to class switching.
What are 3 examples of conjugate vaccines?
- Haemophilus influenzae
type B - MenC
- Pneumococcal conjugate vaccine
For a good antibody response, B cells bind TD Ag via BCR and present the peptide via MHC class 2 molecules to activate CD4+ TH cell. What does CD40 do in this process?
CD40 on B cell binds to CD40 ligand (CD40L) on T cell. Signal two of B cell activation is received when CD40/CD40L bind.
Binding causes T cell to secrete cytokines which are required for class switching. Also, CD40 signal induces activation induced deaminases (AID) which is required for class switching and somatic hypermutation.
CD40 also protects centrocytes from apoptosis.
Once B cells have been activated (TD antigens and TH cells), they move to primary follicles in secondary lymphoid tissues and form germinal centres. What happens in the germinal centres?
B cell proliferation, undergo somatic hypermutation and isotope switching - become CENTROBLASTS
B cells then differentiate into centrocytes - these will then become plasma cells, memory cells or die depending on how high the affinity of BCR is for the antigen.
B cells become centroblasts and then centrocytes in the germinal centres. What is also present in the GCs which help the centrocytes?
Follicular dendritic cells (FDC) - these are not bone marrow derived.
They capture Ag by FcR and complement receptors so that the Ag can bind to the centrocytes.
How do centrocytes become plasma or memory cells?
Centrocytes have BCRs on their surface. The BCRs bind to Ag attached to FDCs. The centrocytes compete for the Ag, and the one which has the highest affinity for the Ag will survive and become a plasma or memory cell.
centrocytes which have undergone somatic hypermutation may have a higher affinity for Ag and therefore will survive.
CD40 expressed by B cells attaches to CD40L on T cells and induces class switching. What happens if there is CD40L deficiency?
Hyper-IgM syndrome. Antibody switching cannot occur so there are only IgMs.
