Deck 6: The Organization and Expression of Lymphocyte Receptor Genes

Question 1

Which of the following BEST encapsulates the findings of the Hozumi and Tonegawa experiments?

A)Every possible light chain that could be formed, in terms of receptor specificity, is encoded by a separate gene within the human genome.
B)Light chains are produced by means of somatic rearrangement of germ-line DNA in B cells.
C)The different light-chain variable regions are produced by means of alternative splicing of pre-mRNA that has been transcribed from a fixed, unchanging DNA sequence.
D)Different light chains, each with unique specificity, are produced via the activity of alternative transcription factors that regulate antibody production at the level of transcription initiation.
E)None of the answers are correct.

Answer 1

B

Question 2

Which of the following gene segments is NOT found in the mouse IgL loci?

A)V
B)J
C)D
D)C
E)All of the answers are found in the mouse IgL loci.

Answer 2

C

Question 3

At which point in the variable segments does the RAG1/2 complex introduce a single-strand break into the DNA during somatic rearrangement?

A)Between the coding region and the conserved heptamer
B)Between the conserved heptamer and the 12-bp spacer
C)Between the 23-bp spacer and the conserved nonamer
D)Between the nonamer and 12-bp spacer
E)None of the answers are correct.

Answer 3

A

Question 4

What introduces a transient hairpin that links the two strands in the V(D)J coding regions?

A)TdT
B)Artemis
C)RAG1/2
D)XRCC4 with DNA ligase IV
E)Ku70/80

Question 5

Several proteins must work in a coordinating fashion to achieve V(D)J recombination.Which is responsible for adding nontemplated nucleotides to the V-D and D-J joints of Ig heavy chains?

A)Artemis
B)RAG1
C)RAG2
D)TdT
E)Ku70/80

Question 6

Which is part of the mature BCR complex but is NOT part of the pre-BCR complex?

A)CD81
B)CD19
C)CD21
D)Ig ?
E)None of the answers are correct.

Question 7

Recognition spacer sequences are separated by how many base pairs?

A)12
B)23
C)7
D)7 or 12
E)12 or 23

Question 8

What binds cut DNA and retains it in protein-DNA complex?

A)TdT
B)Artemis
C)RAG1/2
D)XRCC4 with DNA ligase IV
E)Ku70/80

Question 9

What cleaves interstrand hairpin in V(D)J coding regions?

A)TdT
B)Artemis
C)RAG1/2
D)XRCC4 with DNA ligase IV
E)Ku70/80

Question 10

What introduces single-strand break between V(D)J coding sequence and heptamer RSS?

A)TdT
B)Artemis
C)RAG1/2
D)XRCC4 with DNA ligase IV
E)Ku70/80

Question 11

What introduces nucleotides in a template-independent manner to free 3' OH created upon cleavage of the interstrand hairpin?

A)TdT
B)Artemis
C)RAG1/2
D)XRCC4 with DNA ligase IV
E)Ku70/80

Question 12

Which protein(s) listed below is MOST directly responsible for joining gene segments during V(D)J recombination?

A)RAG1
B)RAG2
C)TdT
D)DNA ligase IV
E)Both RAG1 and RAG2

Question 13

Which protein-encoding genes, although present in genomic DNA, are uniquely expressed by lymphocytes?

A)RAG1
B)RAG2
C)DNA ligase IV
D)TdT
E)RAG1, RAG2, and TdT

Question 14

What closes the final nicks in the sugar-phosphate backbone to generate coding and signal joints?

A)TdT
B)Artemis
C)RAG1/2
D)XRCC4 with DNA ligase IV
E)Ku70/80

Question 15

What recognizes nonamer RSS to begin lymphocyte receptor rearrangement?

A)TdT
B)Artemis
C)RAG1/2
D)XRCC4 with DNA ligase IV
E)Ku70/80

Question 16

Which of the following is NOT a means of generating diversity in the variable regions of the T-cell receptor genes?

A)Cleavage at the coding-heptamer RSS junction by RAG1/2
B)Somatic hypermutation following activation
C)Hairpin cleavage by Artemis to generate P nucleotides
D)Addition of N nucleotides by TdT
E)All of the answers generate diversity in the variable regions of the T-cell receptor genes.

Question 17

How many D ? -J ? rearrangements are possible in a normal human thymocyte?

A)2
B)6
C)4
D)40
E)None of the answers are correct.

Question 18

Which of the following is capable of undergoing successive rearrangements to prevent the formation of autoreactive lymphocyte receptors?

A)IgL ?
B)TCR ?
C)IgH ?
D)Both IgL ? and TCR ?
E)All of the answers are correct.

Question 19

Which of the following IgH chains is NOT produced as a result of CSR?

A) ?
B) ? 1
C) ?
D) ? 2
E)None of the answers are produced as a result of CSR.

Question 20

Which of the following TCR gene variable regions possesses a "D" segment?

A) ?
B) ?
C) ?
D)Both ? and ?
E)All of the answers are correct.

Question 21

Which of the following accounts for allelic exclusion in rearrangement within the IgH locus?

A)Rearrangement only occurs on one homolog at a time, and once one homolog has successfully rearranged, the other is methylated to produce heterochromatin.
B)Rearrangement is regulated by VpreB and ? 5, which are themselves only expressed at specific times during IgH rearrangement
C)Both homologs rearrange simultaneously, undergoing multiple V-J rearrangements until a productive one occurs.
D)All of the answers promote allelic exclusion in IgH.
E)None of the answers are correct; allelic exclusion does not occur in IgH.

Question 22

Which of the following is used to generate diversity in the antibody repertoire?

A)Presence of multiple variable gene segments that can be assembled in multiple different combinations
B)Addition of N nucleotides that are not encoded in the germ line
C)Exonuclease trimming of excess nucleotides at variable segment junctions
D)Ability to pair a single heavy chain with different light chains, so as to avoid generation of autoreactive antibodies
E)All of the answers are correct.

Question 23

Which of the following components that are essential for rearrangement of the IgH and IgL loci are NOT utilized in rearrangement of the TCR loci?

A)RAG1/2
B)Artemis
C)TdT
D)RSS sequences with spacers of 12 bp and 23 bp
E)All of the answers are essential for rearrangement of the TCR loci

Question 24

Which of the following accounts for the transition from membrane-bound IgM to secreted IgM upon activation of a B cell?

A)CSR
B)Affinity maturation
C)Alternative splicing of pre-mRNA
D)Additional modification of nuclear DNA via RAG1/2
E)None of the answers are correct.

Question 25

Deficiency in RAG1 and/or RAG2 can affect the proper development of which of the following cell types, resulting in decreased numbers of circulating cells of those types?

A)B cells
B)T cells
C)NK cells
D)Both B and T cells
E)All of the answers are correct.

Question 26

Consider the following statement from the text, "Immunologists had to face the fact that there simply was not enough DNA to encode all the relevant B-cell receptors, using the one-gene, one-polypeptide chain rule." In one sentence, could you explain, in your own words, what this statement means to a fellow student in your immunology course?

Question 27

Sequencing studies summarized in Figure 6-1 (in the text) demonstrate the existence of antibodies in which the same heavy chain variable region is associated with more than one heavy chain constant region.In your own words, in one sentence, describe the implication of this finding.

Question 28

Dreyer and Bennett proposed that antibody heavy and light chains are encoded in two separate segments in the germ-line genome.At the time, what specifically was so revolutionary about this proposal?

Question 29

Can antibody diversity in humans be explained solely by V(D)J recombination? Why or why not?

Question 30

Do you think, after reading this chapter, the statement that all human cells in an individual contain the same genome is true or false?

Question 31

V(D)J recombination involves a significant number of proteins, working together in a coordinated fashion.Can you think of two potential reasons why so many proteins are involved?

Question 32

Taking into consideration the length of bases between recombination sequences, can you describe the functional significance of the lengths?

Question 33

Expression of RAG1 and RAG2 is tightly regulated.In addition to limiting the expression of RAG1 and RAG2 to select lymphocytes, can you describe a mechanism used to regulate the activity of RAG1 and RAG2 at the protein level?

Question 34

If a given B cell is found to be potentially reactive to self-antigens, can the cell make an effort to correct that flaw, or is it destined for eventual removal by apoptosis?

Question 35

Imagine a lymphocyte is actively undergoing V(D)J recombination.V(D)J recombination has reached a stage where alleles are being excluded from expression.Within the nucleus, where would you expect to find the excluded alleles, and why?