52. Humoral Immunity, B Cell Activation, Affinity

Question 1

Antibody functions

Answer 1

1) Virus & toxin neutralization ~ Prevents pathogen-host binding
2) Opsonization + ADCP ~ Phagocytosis
3) Complement fixing/MAC formation (CDC) ~ Phagocytosis or lysis
4) Opsonization + ADCC ~ NK-induced apoptosis

Question 2

What are the different classes of antibodies?

Answer 2

• IgG
• IgD
• IgA
• IgE
• IgM

Question 3

Expand on B cell activation

Answer 3

• Differentiation and clonal expansion of activated B cells
• Requires 3 signals
  • Antigen binding to BCRs
  • Co-stimulation by activated Th cell specific to same antigen
  • Th cell-derived cytokines

•Signal transduction pathway

Question 4

Signal transduction pathways

Answer 4

• BCR binding > Activation of tyrosine kinase

* Signal transduction pathway for cell proliferation, differentiation and survival

Question 5

Describe the events of clonal expansion

Answer 5

• Body produces many B cells with unique BCRs
• When there is a pathogen, the B cells that binds the pathogen the closes will be activated and make more clones of itself and these clones will migrate to the germinal centre for affinity maturation

Question 6

What happens in affinity maturation?

Answer 6

• There is a low affinity antibody
• This undergoes somatic mutations in variable regions - by AID (activation-induced cytidine deaminase)
• Leads to selection of high-affinity B cells
• This will migrate to the light zone, where the FDC will present antigens on the surface, B cells with high enough affinity will try to take as much antigens from its surface and present to the Tfh cells
• The Tfh cells will give the survival signal
• The reduced affinity B cells will undergo apoptosis in the light zone

•You repeat this several times until the affinity is high enough and then you go to the class switching stage

Question 7

Affinity maturation and class switching in Germinal Centre

Answer 7

1) Clonal expansion
2) Somatic hypermutation
3) Repeats until improved affinity (the disadvantageous mutations lead to apoptotic B cell)
4) Selection
5) Class switching - memory B cells and plasma cells
6) Differentiation

Question 8

Heavy chain class switching

Answer 8

• Only affects heavy chain CONSTANT region
• Different effector functions – deal with different pathogens

• MINOR: Differential splicing (mRNA level)
- IgM and IgD (last lecture)

• MAJOR: DNA recombination

• IgM to IgG, IgA, IgE
• IgG to IgA, IgE

•Class switching is mediated by cytokine signalling

Question 9

Class switch recombination (CSR)

Answer 9

• 1) Cytokine signal; 2) Switch regions; 3) AID and DSB repair proteins
• Recombination between switch regions
• Switching only proceeds downstream
• IgM to IgG, IgA, IgE
• IgG to IgA, IgE

Question 10

What is the difference between membrane and secreted antibody?

Answer 10

SECRETED IgG
- Has tail piece

MEMBRANE IgG
- Has membrane anchor made of hydrophobic transmembrane region and cytoplasmic tail