Humoral Immunity - B cell activation, affinity maturation and class switching

Question 1

Summarise the processes which occur in the antigen dependant phase of the B-cell life cycle

Answer 1

• We will have the mature B-cell expressing IgM and IgD through differential splicing
• T helper cells will activate B-cell during an infection
• Activated B cells will migrate to the germinal centre (GC) to undergo affinity maturation
  
  • This will involve clonal expansion and somatic hypermutation (dark zone)
  • They will then migrate to the light zone where they undergo selection
    
    • This process will be repeated many times
• The antibody will then recieve signals to tell them what type of antibody they are fighting and undergo class switching (so they have the appropriate effector functions)
• After that the B-cell will differentiate to plasma cells secreting antibodies whilst maintaining some B-cell receptors on their surface
• A few will become memory B-cells

Question 2

What are the two stages of B-cell activation?

Answer 2

• T cell independent stage B cell activation
• T-cell dependant B-cell activation

(Not to be confused with the antigen dependant and antigen independant phases of the B-cell life cycle)

Question 3

Describe what occurs in T cell independant stage B cell activation

Answer 3

1. Pathogen will invade and a B-cell will be partially activated when it binds to and processes the antigens
2. The B-cell will make clones of itself through clonal expansion
3. This will become the 1st defence army secreting IgM to hold off pathogen invasion
4. The other clones will migrate to the lymph node and await T-cell activation

Question 4

Describe the process occuring in T-cell dependant B-cell activation

Answer 4

1. Some of the B-cell clones will have migrated to the lymph node to await T-cell activation in the T-cell independant B-cell activation stage
2. The T-cell dependant B-cell activation stage requires triple verification to ensure B-cells do not get activated by mistake
   
   1. Antigen binding to BCR
   2. Antigen will be present on the surface of B-cells via the MHC II receptor recognised by the activated T helper cell via TCR
      
      1. T-helper needs to be activated by same pathogen through dendritic cells
      2. There is also a CD40/CD40L handshake to confirm that this is a T-helper cell
   3. Cytokines will be produced by the T-helper cell
3. Fully activated B cells will undergo affinity maturation and class switching differentiating into plasma cells secreting antibodies

Question 5

What does binding of the antigen to the B cell receptor (BCR) lead to?

Answer 5

Activation of protein tyrosine kinases

This will lead to phosphorylation of downstream proteins in a signal transduction pathway for cell proliferation, differentiation and survival

Question 6

What is affinity maturation?

What is its purpose?

Answer 6

Affinity maturation is the fine tuning of the antibody affinity to the antigen

This occurs through mutations in the variable region genes and selection of the antibody with the highest affinity

• The antigen binding following V(D)J recombination is at a low affinity
  
  • The antigen will take longer to bind + bind more loosely to the antibody

Question 7

Where does affinity maturation take place?

Answer 7

• Takes place in the germinal centre (GC) of the lymph node
  
  • GCs are circular cell clusters in the periphery of the lymph node

Question 8

What are the two types of cells which will help with the process of affinity maturation?

Answer 8

1. T follicular helper cells (Tfh)
2. Follicular Dendritic Cells (FDC)

Question 9

What processes occur during affinity maturation?

Answer 9

Clonal expansion, Somatic Hypermutation and Selection

Question 10

Describe the process of affinity maturation

Answer 10

1. Activated B-cells will enter GC and undergo clonal expansion in dark zone
2. Somatic hypermutation occurs through AID (activation induced cytidine deaminase) generating point mutations in V. region gene of B-cells
   
   1. All of the B-cells which were clones are now slightly different
3. Hypermutated B-cells undergo selection in light zone
   
   1. FDC (follicular dendritic cells) will present antigens on its surface and B-cells will need to compete for limited amount of antigens on FDC
   2. B-cells able to bind to antigens on FDC will grab as many antigens as they can + present them to Tfh = survival signal
      
      1. Different from the Th cells which activated B-cells initially
4. Cells that have a reduced affinity to the antigens on the FDC will die as they do not recieve the survival signals from Tfh
5. B-cells surviving the process will migrate back to the dark zone and the process will begin again until the antibody affinity is high enough

Question 11

What enzyme is involved in the process of somatic hypermutation in the affinity maturation process?

Answer 11

AID (Activation-induced cytidine deaminase)