Lecture 3 - Antibody Genetics Flashcards
What Ig subclasses are found on naive B cells?
M and D. They are like residents. Naive MDs.
What Ig subclasses are found on mature B cells?
G, A, E. They have come out, and they are GAE.
Where does V(D)J recombination occur?
In the primary lymphoid organs.
What are RAG-1 and RAG-2?
Proteins required by lymphocytes for V(D)J recombination.
Do the IgM and IgD antibodies present on on a single naive B cell have specificity for the same antigen?
Yes.
What two things account for the majority of the diversity of antibodies?
Junctional imprecision and somatic hypermutation (SHM)
Describe Junctional imprecision.
When the Vs, Ds, and Js are joined by B lymphocytes, random nucleotides are excised and added by exonucleases and TdT (terminal deoxyribonucleotidyl transferase), respectively.
What is TdT involved in?
Adding nucleotides randomly during VDJ recombination.
Does somatic hypermutation occer before or after antigen stimulation?
After
What is somatic hypermutation (SHM) and what does it result in?
SHM is rapid point mutations in the variable region genes after antigen stimulation. This leads to slightly mutated antibodies with different affinities for the antigen. Those with higher affinity will bind the antigen better, and will subsequently clonally expand. This results in 100-1000 fold increase in Ig affinity.
When does class switching occur?
After antigen stimulation.
What is the point of the pentameric IgM?
It is the body’s way of making an Ig right away that has somewhat high affinity for a pathogen. SHM takes some time to occur. An Ig complex with 10 low-affinity binding sites is better than one Ig with two low-affinity binding sites.
What is activation-induced cytidine deaminase (AID)? What disease results from a non-existent or defective AID?
It is a protein that mediates CSR and SHM. Deficient folks have hyper-IgM syndrome.
How many light chain isotypes are there? What are the names? Which one is more common?
Two - kappa and lambda. Kappa is more common.
