CHAPTER 4
Antibody Structure and the Generation of B-Cell Diversity
Questions
4–1
How do recombination signal sequences ensure that gene segment rearrangement occurs
in the right order?
4–2
How is additional diversity introduced into the variable region by the molecular
mechanism of somatic recombination? Include the following terms in your answer:
junctional diversity, P nucleotides, N nucleotides, terminal deoxynucleotidyl transferase
(TdT).
4–3
Explain how mature, naive B cells co-express IgM and IgD.
4–4
Describe the process responsible for altering the expression of membrane-bound
immunoglobulin to secreted antibody.
4–5
A. What is affinity maturation and what molecular process enables it to occur?
B. Describe this process and its consequences.
4–6
A. What is isotype switching?
B. Explain the molecular mechanism of isotype switching.
C. Why is isotype switching important?
4–7
Which immunoglobulin isotypes (out of IgM, IgG1, IgG2, IgG3, IgG4, IgA, IgE, and
IgD) participate in (a) neutralization; (b) opsonization; (c) sensitization for killing by NK
cells; (d) sensitization of mast cells; (e) activation of complement? Which isotypes (f) are
transported across epithelium; (g) are transported across the placenta; (h) diffuse into
extravascular sites?
4–8
2
Isotype switching and immunoglobulin gene rearrangement by somatic recombination are
both recombinational processes but have very different outcomes. Give four ways in
which they differ from each other.
4–9
Monoclonal antibodies are used for a wide range of applications including serological
assays and diagnostics probes in the laboratory, and as therapeutic reagents in the clinic.
Discuss why ‘humanizing’ monoclonal antibodies is necessary for use as therapeutic
reagents but is not necessary when monoclonal antibodies are used as serological or
diagnostic reagents.
4–10
What would be the effect of a genetic defect that resulted in a lack of recombination
between the switch regions in the immunoglobulin C-region genes?
4–11
Influenza virus contains two proteins, called hemagglutinin and neuraminidase, exposed
on the surface of the virion. Two additional proteins, located on the interior of the virion,
are called matrix protein and nucleoprotein. Which of these four proteins will generate a
better antibody response and why?
4–12
A. Identify the four types of antibodies used for therapeutic purposes.
B. How is each produced?
C. (i) Which is most desirable for the treatment of chronic conditions and (ii) why?
(iii) Provide an example.
4–13
Which of the following does not describe B-cell receptors?
a. B-cell receptors are membrane bound and secreted.
b. B-cell receptors consist of a variable region and a constant region.
c. B-cell receptors lack specificity and can bind to a number of different antigens.
d. B-cell receptors possess specificity and can therefore bind only to unique
epitopes.
e. B cell receptors undergo affinity maturation as a consequence of somatic
hypermutation.
4–14
A. What is the difference between polyclonal antibodies and monoclonal antibodies?
B. How is each produced?
4–15
The five classes (isotypes) of immunoglobulins include:
a. IgA, IgD, IgE, IgG, IgM
b. IgA, IgC, IgD, IgE, IgG
c. IgA, IgD, IgE, IgH, IgM
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d. IgA, IgD, IgE, IgG, IgK
e. IgA, IgD, IgE, IgG, IgS.
4–16
The name given to a fully activated and differentiated B cell that secretes antibody is:
a. T cell
b. antigen-presenting cell
c. hematopoietic cell
d. secretory cell
e. plasma cell.
4–17
The antigen-binding site of an immunoglobulin is formed from:
a. the V regions of light chains only
b. the C regions of heavy chains only
c. paired V regions of a single heavy chain and a single light chain
d. paired V regions of two light chains
e. paired C regions of two heavy chains.
4–18
The _______ contribute to antigen specificity of immunoglobulins, and _______ make up
the more conservative flanking regions:
a. hypervariable loops; framework regions
b. constant domains; variable domains
c. heavy chains; light chains
d. variable gene segments; joining gene segments
e. antigenic determinants; complementarity determining regions.
4–19
Which of the following corresponds to the antigen binding site of immunoglobulins?
a. VH:CH
b. VH:VL
c. VL:CL
d. CH:CL
e. VH:CL.
4–20
A protein epitope formed as a result of three-dimensional folding of the protein, and
which is destroyed if the protein denatures, is called a _______ epitope:
a. linear
b. multivalent
c. conformational
d. complementarity
e. framework.
For questions 4–21 through 4–25 below, select one of the following answers:
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a. monoclonal antibody production
b. isotype switching
c. somatic hypermutation
d. opsonization
e. somatic recombination.
4–21
__The rearrangement of V, D, and J segments to form an immunoglobulin.
4–22
__ The derivation of antibodies from a single clone of B lymphocytes that have identical
antigen specificity.
4–23
__ Change of immunoglobulin class but preservation of antigen specificity.
4–24
__ Nucleotide changes in variable regions of immunoglobulin genes affecting affinity for
antigen.
4–25
__ Enhancement of receptor-mediated phagocytosis of immunoglobulin-coated antigen.
4–26
The immunoglobulin heavy-chain gene consists of _______ segments, whereas the
immunoglobulin light-chain gene consists of _______ segments.
a. ;
b. VDJ; VJ
c. VJ; VDJ
d. P; N
e. RAG-1; RAG-2.
4–27
On the heavy-chain immunoglobulin gene locus, recombination signal sequences flank
_______ of the V segment, _______ of the D segment, and _______ of the J segment.
a. the 5 side; both sides; the 3 side
b. the 5 side; the 5 side, the 5 side
c. the 3 side; both sides; the 3 side
d. both sides; both sides; both sides
e. the 3 side; both sides; the 5 side.
4–28
Which of the following describes two recombination signal sequences required for a
permitted somatic recombination event?
a. VH 7-12-9::9-23-7 JH
b. V 7-23-9::9-23-7 J
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c. DH 7-12-9::9-23-7 JH
d. V 7-12-9::7-23-9 J
e. VH 9-23-7::7-12-9 DH.
4–29
The enzyme responsible for recombining V, D, and J segments during somatic
recombination is called:
a. V(D)J recombinase
b. Terminal deoxynucleotidyl transferase
c. Exonuclease
d. DNA polymerase
e. DNA ligase.
4–30
IgM and IgD are co-expressed on naive B cells by a process called:
a. isotype switching
b. somatic recombination
c. somatic hypermutation
d. alternative mRNA splicing
e. affinity maturation.
4–31
Which immunoglobulin’s main function is to mediate sensitization of mast cells?
a. IgA
b. IgD
c. IgE
d. IgG
e. IgM.
4–32
Which immunoglobulin is transported most efficiently across mucosal epithelium?
a. IgA
b. IgD
c. IgE
d. IgG
e. IgM.
4–33
_______ forms dimers, whereas _______ forms pentamers:
a. IgG; IgD
b. IgE; IgM
c. IgD; IgM
d. IgA; IgM
e. IgM; IgG.
4–34
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A newborn derives passive immunity from its mother as a result of placental transfer of
_____ during pregnancy:
a. IgA
b. IgD
c. IgE
d. IgG
e. IgM.
4–35
_____ is secreted into the bloodstream, whereas _____ is secreted into mucus such as
gastrointestinal fluid, colostrum, saliva, tears, and sweat:
a. Monomeric IgM: pentameric IgM
b. Monomeric IgA: dimeric IgA
c. Monomeric IgA: dimeric IgG
d. Monomeric IgA: monomeric IgM
e. Dimeric IgA: pentameric IgM.
4–36
Which of the following is not a component of V(D)J recombinase?
a. Artemis
b. Terminal deoxynucleotidyl transferase
c. RAG-1/RAG-2
d. DNA ligase IV
e. DNA-dependent protein kinase and the associated Ku protein.
4–37
Identify which of the following is not associated with activation-induced cytidine
deaminase (AID) activity:
a. diversification of the VH domain but not the VL domain
b. synthesized in proliferating B cells during active immune responses
c. somatic hypermutation
d. isotype switching
e. cytosine conversion to uracil.
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Answers
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