Development of B Cell Diversity

Question 1

Explain the clonal selection theory?

Answer 1

Each native B -cell produce an immunoglobulin of unique specificity

Question 2

What are the practical implications of the clonal selection theory?

Answer 2

The number of binding specificites must be very large, too large to be encoded for within the DNA

Question 3

What are the rearrangeable units of light chains?

Answer 3

V and J regions

Question 4

What are the rearrangeable units of heavy chains?

Answer 4

V, D, and J regions

Question 5

What is used to recombine these variable regions?

Answer 5

RAG proteins and recombination signal sequences

Question 6

Which variable region is closes to the constant region of light chains?

Answer 6

J region

Question 7

How big is the J region?

Answer 7

10-13 AA long

Question 8

In which Ig producing B cells does the J region change position? And what are the implication of this position change?

Answer 8

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

Question 9

How big is the D segment?

Answer 9

2-8 amino acids

Question 10

Constant regions for the light chain?

Answer 10

kappa and lambda

Question 11

Which light chain is rearranged first?

Answer 11

kappa, on both chromosomes. if it fails then cell tries lambda on both chromosomes

Question 12

What is the recombination order of the light chain?

Answer 12

Germline DNA undergoes somatic recombination and the VJ segments are joined to form rearranged DNA.

Question 13

What is the recombination order of the heavy chain?

Answer 13

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.

Question 14

Are the VJ and VJD rearrangements permanent?

Answer 14

Yes. Because the RAG proteins excise the DNA to form the recombinations.

Question 15

What increases the variability during joining?

Answer 15

The fact that joining is imprecise

Question 16

What makes a functional gene?

Answer 16

Rearrangements and nucleotide insertions

Question 17

Imprecise joining of V to J (in light chains) results in…

Answer 17

addition of 4 nucleitides to result in an “in frame” shift

Question 18

What does the joining of D to J and V-DJ in heavy chains result it?

Answer 18

Addition of nucleotides can result in multiple reading frames

Question 19

Where is the checkpoint in heavy chain rearrangement?

Answer 19

v-DJ rearrangement

Question 20

Where are P nucelotides found?

Answer 20

Found on all joining junctions in B and t cells

Question 21

What is a P nucleotide sequence?

Answer 21

A palandromic sequence typically

Question 22

Where are N nucleotides found?

Answer 22

Found only in developing B cell Heavy Chains

Question 23

What is class switching?

Answer 23

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.

Question 24

What chain undergoes somatic recombination first?

Answer 24

Heavy chain

Question 25

When does class switching occur?

Answer 25

After activation of a mature B cell

Question 26

When does a B cell become mature?

Answer 26

When it is in the lymph node

Question 27

What do naive B cells express on their surface?

Answer 27

They express IgM (first) and then IgD.

Question 28

How is IgD formed?

Answer 28

Selectively splicing of an RNA. It is not class switching because no DNA is being looped out.

Question 29

Is class swithcing reversible?

Answer 29

No it is not because DNA is looped out via DNA splicing.

Question 30

What mediates class switching?

Answer 30

Not RAG

Question 31

What are the two aspects of Ig that are controlled by RNA splicing?

Answer 31

IgM vs. IgD a

Membrane bound Ig or secreted Ig

Question 32

What is somatic hypermutation?

Answer 32

Mutations that take place during an immune response in the entire variable domain. It is random single base mutations.

Question 33

What cells undergo somatic hypermutation?

Answer 33

B cells only, not T cells

Question 34

What mediates the addition of N nucleotides?

Answer 34

TdT, an enzyme found only in developing B cells in the proB stage