Lecture 22- somatic hypermutation, affinity maturation and class- switching in B cells. Flashcards
What is the result of CD40 signalling from the Tfh cell to the B cell?
- B cell proliferation
- expression of activation-induced cytosine deaminase (AID)
What is the function of AID?
- somatic hypermutation (point)
- Class (or isotype) switching. (excision of DNA)
Where does somatic hypermutation occur? Where does class switching occur?
- dark zone during proliferation
- light zone
How does class switching differ from somatic recombination?
similar process, still excise DNA, but no VDJ recombination
What is somatic hypermutation?
AID is a DNA deaminase, and removes an amino group from cytosines (C) in a single stranded template and converts it to deaminated uracil (U)
When are hypermutations introduced to the DNA?
When the DNA is being replicated
How many rounds of DNA replication does it take for the mutation to be stabilized?
2 rounds
What is the function of UNG? (uracil-DNA glycosylase)
excise the uracil base to create an abasic site in the DNA (take out the base for DNA repair processes to make a substitution)
Why is antigen only present in low amounts in the germinal centre?
It is being consumed by FDCs
Can the B cell go back and forth between the dark and light zone for hypermutation?
yes
Where does most of the isotype switching occur (specifically)?
germinal centres
What is isotype switching?
Involves only the heavy chain genes and generates antibodies
of different classes; the different classes of antibodies perform distinct effector
functions. The specificity of the antibody remains the same.
What regulates isotype switching?
Th cytokines