B cell development

Question 1

What regions make up the variable region of a heavy chain?

Answer 1

J region, V region, D region

Question 2

What regions make up the variable region of a light chain?

Answer 2

J region, V region

Question 3

How is diversity brought to Ab?

Answer 3

random combination of J, V, and D
junctional diversity
random combination of light chain and heavy chain

Question 4

Describe the process of recombination of light chain.

Answer 4

A V region and a J region are brought together via somatic recombination. Two regions are brought close together by a loop forming and being excised, followed by nucleotide insertions.

Question 5

In what order do JVD come together on heavy chains?

Answer 5

D and J brought together first. V brought to the DJ complex. Nucleotide insertions connect the two segments as they are joining.

Question 6

How are segments within the variable regions brought together?

Answer 6

RAG- recombinase genes bind certain sequences and pull the ends together to form the loop that gets excised

Question 7

What is a signal joint? Where is in it?

Answer 7

the DNA between the V, D, or J segments that are being joined that is excised and eventually degrades, in the lariat

Question 8

How are the V and J regions joined in light chains?

Answer 8

• involves 4 different codons to create “in frame” gene sequence coding for variable light chain
• RAG complex opens hairpins of DNA to generate palindromic P nucleotides

Question 9

How are the V and DJ regions joined in heavy chains?

Answer 9

• RAG snips DNA, there are variable strands of NT bases left
• TdT adds random AAs (N nucleotides) on the free ends of DNA
• eventually overlap exists so repair enzymes can mend the strands together

Question 10

When does terminal deoxynucleotidyl transferase exist?

Answer 10

during heavy chain arrangement only

Question 11

What are two examples of non-functional rearrangments made by TdT?

Answer 11

• reading frame shift if the number of AA generated is not divisible by 3
• inserting stop codon

Question 12

What is an early proB cell?

Answer 12

DJ heavy chain rearrangements on both chromosomes

Question 13

What is a late proB cell? (checkpoint 1)

Answer 13

V-DJ rearrangement on 1st chromosome, if fails, V-DJ rearrangement on 2nd chromosome
-if it fails to put heavy chain on membrane in certain time to interact with surrogate light chain, it will apoptose

Question 14

What is a preB cell?

Answer 14

Rearrange Kappa on 1st chromosome, if it fails, rearrange Kappa on 2nd chromosome, Lambda on 1st chromsome, Lambda on 2nd chromosome, then will apoptose

Question 15

When is there a surrogate light chain? What does it signal?

Answer 15

It is in the pre Bcell stage to see if functional heavy chain has been produced. It signals light chain rearrangement if heavy chain rearrangement was successful or apoptosis if not.

Question 16

How do you class switch from IgM to IgD?

Answer 16

Selective splicing of primary RNA transcript

Question 17

Can you have IgM and IgD produced by the same cell?

Answer 17

Yes, signals in the environment can affect the splicing of RNA

Question 18

Which constant region exon is for IgM and IgD?

Answer 18

mu for IgM, delta for IgD

Question 19

How is secreted vs. membrane bound form of Ab determined?

Answer 19

alternative splicing of primary RNA transcript (same mechanism as IgM to IgD)
- 2 extra exons included for longer transmembrane form

Question 20

Which form of Ab do active B cells produce: secreted or membrane bound?

Answer 20

secreted

Question 21

How do you class switch from IgM to IgG? Is it permanent?

Answer 21

• DNA splicing form the same transcript due to signals from the environment
• variable region is joined to a new constant chain
• it is permanent

Question 22

What chain is involved in class switch from IgM to IgG?

Answer 22

• constant regions brought together to form different heavy chains
• heavy chain switches

Question 23

Is class switch regulated by RAG?

Answer 23

no

Question 24

What enzyme mediates class switch and somatic hypermutation?

Answer 24

AID- activation-induced cytidine deaminase

Question 25

What region and specific sites within it experience alteration during somatic mutation? Why?

Answer 25

• variable region
• CDR1 and CDR2 (along with CDR3 are contact residues of Ag)
• yields improved binding to Ag they are selected for

Question 26

When is the mutation frequency highest in the immune response?

Answer 26

• when B cells is most stimulated by T cells, as it undergoes class switch
• select B cells for with mutations in hypervariable region that binds better

Question 27

What is different in T cell receptor formation from B cell? Why?

Answer 27

• somatic hypermutation

- educated in thymus not to recognize self and don’t want to mutate to lose that self-recognition

Question 28

What enzymes do both T cell and B cell receptor development processes use?

Answer 28

TdT and RAG

Question 29

If you lack RAG, what effects will that have on the immune system?

Answer 29

No T cells or B cells properly rearranged, will be immunodeficient