L3: Antibody Diversity/B cell development

Question 1

What is the first step in B cell development?

Answer 1

rearrange the Ig genes that code for the heavy and light chain that make up the Ig that is made by that B cell. IgM is then expressed on the surface of the B cell.

Question 2

What is the first Ig that all B cells present?

Answer 2

IgM

Question 3

What is the first type of Ab produced after B cells are activated?

Answer 3

pentameric IgM antibodies

Question 4

True of False: each Ig molecule produced by any one B cell is identical.

Answer 4

True

Question 5

What is the antibody repertoire?

Answer 5

The complete collection of antibody BCR specificities generated by somatic recombination

Question 6

Does production of B cells in bone marrow depend on antigen presentation?

Answer 6

No. Somatic recombination is totally antigen-independent. They do not see antigens until they are in secondary lymph tissue

Question 7

What do RAG-1 and RAG-2 do? What happens if you have a defect in either?

Answer 7

RAG-1 and RAG-2 are reactivation activation genes; enzymes that mediate somatic recombination. You will not be able to make functional lymphocytes.

Question 8

How many Ig domains does each light chain have?

Answer 8

2. One constant and one variable

Question 9

How is heavy chain organization different from K light chains?

Answer 9

It has a D region in between the Variable region and J region.
Order: Variablle, D region, J region, Constant

Question 10

Describe the organization of Lambda light chains.

Answer 10

Variable region, J region, Constant, J-region, constant, j region, constant

Question 11

Describe the organization of K light chains?

Answer 11

variable, J region, constant

Question 12

What is the first constant region in all Ig’s?

Answer 12

Mu chain, which codes for IgM, which is why it is always the first to be produced.

Question 13

Which takes place first: light chain or heavy chain rearrangement?

Answer 13

Heavy chain rearrangement always occurs first in all developing B cells

Question 14

What is the effect of only having one of each pair of chromosomes rearrange?

Answer 14

It ensures each B cell only codes for one specificity.

Question 15

What segments are paired to make lambda and K light chains?

Answer 15

V and J segments

Question 16

What segments are paired to give rise to heavy chains?

Answer 16

V, D, and J segments

Question 17

Why is the imprecise nature of somatic recombination important?

Answer 17

Along with the recombination of heavy and light chains, it allows for massive variability from a handful of genes.

Question 18

What percentage of B cells express antibodies that have both kappa and lambda light chains?

Answer 18

0%. B cells can only produce Abs with one specificity.

Question 19

What is the order of heavy chains on Ig?

Answer 19

This WILL be on exam
Mu (IgM), delta (IgD), gamma3 (IgG3), gamma1 (IgG1), psuedo gene (nonfunct), A1 (IgA1), gamma2 (IgG2), gamma4 (IgG4), epsilon (IgE), A2 (IgA2)

Question 20

Which is the only heavy chain region that doesnt have a switch region before it?

Answer 20

IgD

Question 21

What is affinity maturation?

Answer 21

mutation that occurs at high frequency in the rearranged variable-region DNA of Ig genes in activated B cells, resulting in the production of varient antibodies, some of which have higher affinity for the antigen. Occures in follicles in secondary lymphoid tissues. B cells that express higher affinity Abs are positively selected. (antigen-dependent process)

Question 22

What is IL-7 and what happens if it is defective?

Answer 22

It is a cytokine released from bone marrow stroma that is necessary for B cell production. Without it, it is impossible to develop a B cell repetoire

Question 23

Describe the steps of Naive B cell production.

Answer 23

Lymphoid progenitor made in bone marrow; becomes early pro-B cell; D-J rearranging to make late pro-B cell; V-DJ rearranging to form Large pre-B cell; heavy chain translation and presentation of heavy chains;V-J rearranging of light chain; expression of IgM on surface; IgD starts to appear and cell is now a Mature B cell.

Question 24

What is Bruton’s thymidine kinase (Btk)? What happens when it is deficient?

Answer 24

enzyme involved in signal transduction from cell-surface receptors during B cell development.
Without it, very small B-cell repertoire.

Question 25

What enzyme(s) make double-stranded breaks in DNA during somatic recombination? What happens without them?

Answer 25

RAG-1 and RAG-2.

without them you wont have B or T cells

Question 26

Which enzyme catalyzes the addition of N nucleotides at the junctions between rearranging gene segments?

Answer 26

TdT (terminal deoxynucleotidyl transferase)

Question 27

What is AID? What type of Ig would you expect to be the most common in cells produced by an individual with a defect in AID?

Answer 27

activation-induced cytidine deaminase: enzyme that catalyzes class switching. It is also required for somatic hypermutation (Affinity maturation).

There would only be IgM because nothing would be able to class switch.

Question 28

Where are most self-recognizing B cells found and terminated?

Answer 28

While they are still in the bone-marrow.

Question 29

What does it mean for a cell to become anergic?

Answer 29

Its surface becomes dominated by IgD and has trouble reacting with anything. It quickly dies.

Question 30

Which of the following DOES NOT contribute to the diversity of the B cell repertoire?
pairing of different light and heavy chains
isotype switching
somatic recombination
affinity maturation
imprecise DNA joining during somatic recombination

Answer 30

isotype switching. Just changes function of Ig, not specificity.