Development of B Cell Diversity Flashcards
Explain the clonal selection theory?
Each native B -cell produce an immunoglobulin of unique specificity
What are the practical implications of the clonal selection theory?
The number of binding specificites must be very large, too large to be encoded for within the DNA
What are the rearrangeable units of light chains?
V and J regions
What are the rearrangeable units of heavy chains?
V, D, and J regions
What is used to recombine these variable regions?
RAG proteins and recombination signal sequences
Which variable region is closes to the constant region of light chains?
J region
How big is the J region?
10-13 AA long
In which Ig producing B cells does the J region change position? And what are the implication of this position change?
It DOES NOT change position in IgM and IgD B cells, but it DOES change position in IgE, IgA and IgG
This means that the DNA was rearranged
How big is the D segment?
2-8 amino acids
Constant regions for the light chain?
kappa and lambda
Which light chain is rearranged first?
kappa, on both chromosomes. if it fails then cell tries lambda on both chromosomes
What is the recombination order of the light chain?
Germline DNA undergoes somatic recombination and the VJ segments are joined to form rearranged DNA.
What is the recombination order of the heavy chain?
Germline DNA undergoes somatic recombination and the DJ segments are joined. A second somatic recombination even occurs that joins the V to the DJ segment. The result of all this is the VDJjoined rearranged segment.
Are the VJ and VJD rearrangements permanent?
Yes. Because the RAG proteins excise the DNA to form the recombinations.
What increases the variability during joining?
The fact that joining is imprecise
What makes a functional gene?
Rearrangements and nucleotide insertions
Imprecise joining of V to J (in light chains) results in…
addition of 4 nucleitides to result in an “in frame” shift
What does the joining of D to J and V-DJ in heavy chains result it?
Addition of nucleotides can result in multiple reading frames
Where is the checkpoint in heavy chain rearrangement?
v-DJ rearrangement
Where are P nucelotides found?
Found on all joining junctions in B and t cells
What is a P nucleotide sequence?
A palandromic sequence typically
Where are N nucleotides found?
Found only in developing B cell Heavy Chains
What is class switching?
Constant region heavy portion is changed and the variable region stays the same. As a result the antibody’s specificity does not change. However, the antibody can now interact with different effector molecules.
What chain undergoes somatic recombination first?
Heavy chain
When does class switching occur?
After activation of a mature B cell
When does a B cell become mature?
When it is in the lymph node
What do naive B cells express on their surface?
They express IgM (first) and then IgD.
How is IgD formed?
Selectively splicing of an RNA. It is not class switching because no DNA is being looped out.
Is class swithcing reversible?
No it is not because DNA is looped out via DNA splicing.
What mediates class switching?
Not RAG
What are the two aspects of Ig that are controlled by RNA splicing?
IgM vs. IgD a
Membrane bound Ig or secreted Ig
What is somatic hypermutation?
Mutations that take place during an immune response in the entire variable domain. It is random single base mutations.
What cells undergo somatic hypermutation?
B cells only, not T cells
What mediates the addition of N nucleotides?
TdT, an enzyme found only in developing B cells in the proB stage
