CHAPTER 6
The Development of B Lymphocytes
Questions
6–1
Describe the six functionally distinct phases of B-cell development.
6–2
Which of the following cell-surface markers differentiates hematopoietic stem cells from other
cell constituents in the bone marrow?
a. pre-B-cell receptor
b. BAFF receptor
c. CD34
d. CD4
e. membrane-bound stem-cell factor (SCF).
6–3
Which of the following is characteristic of a large pre-B cell?
a. VDJ is successfully rearranged and heavy chain is made.
b. V–J is rearranging at the light-chain locus.
c. heavy chain and or light chain is made.
d. V is rearranging to DJ at the heavy-chain locus.
e. D–J is rearranging at the heavy-chain locus.
6–4
Which of the following statements is correct?
a. The light-chain genes rearrange before the heavy-chain genes.
b. The light-chain genes rearrange before the light-chain genes.
c. The light-chain genes rearrange before the heavy-chain genes.
d. The light-chain genes rearrange before the light-chain genes.
e. The heavy-chain genes rearrange first and then the light-chain genes rearrange.
6–5
Stromal cells produce _______, which is a secreted B-cell development growth factor
influencing the progression of B cells from the late pro-B-cell to the pre-B-cell stage:
a. stem-cell factor
b. Kit
c. IL-7
d. VLA-4
e. VCAM-1.
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6–6
Immature B cells develop into B cells in the
a. subendosteum.
b. bone marrow.
c. thymus.
d. blood.
e. secondary lymphoid organs.
6–7
Developing B cells that fail to make productive D to J heavy-chain rearrangements on both
homologous chromosomes
a. die by apoptosis in the bone marrow.
b. will rearrange heavy-chain loci multiple times until a productive rearrangement is made.
c. undergo clonal proliferation.
d. upregulate expression of transcription factors E2A and EBF.
e. fail to rearrange V to DJ.
6–8
Pro-B cells produce a surrogate light chain, which associates with the chain on the cell surface.
The surrogate light chain is composed of
a. E2A and EFB.
b. Ig and Ig.
c. VpreB and 5.
d. RAG-1 and RAG-2.
e. Pax5 and CD19.
6–9
A genetic defect in the \lambda5 gene would cause which of the following consequences? (Select
all that apply.)
a. inability to produce functional chains
b. inability to produce a pre-B-cell receptor
c. inability to produce functional or chains
d. production of different light chains owing to defects in allelic exclusion
e. B-cell immunodeficiency
f. chronic bacterial infections
g. a requirement for prophylactic injections of antibodies from healthy donors.
6–10
When producing monoclonal antibodies, why is it important to use as a fusion partner a myeloma
cell that is unable to produce its own immunoglobulin?
a. To ensure that allelic exclusion of \mu chain occurs normally.
b. To ensure that the antibodies are homogeneous and able to make strong bivalent
attachments to multivalent antigens.
c. To ensure that the monoclonal antibodies are not autoreactive.
d. To provide a greater opportunity for making a successful rearrangement at the light-chain
locus.
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e. To ensure that antibodies are secreted and not membrane-bound.
6–11
An important advantage of having two gene loci ( and ) for the light chain is
a. that the likelihood of a successful rearrangement of light-chain genes increases.
b. that immunoglobulins are homogeneous and not heterogeneous in mature B cells.
c. that different effector functions are conferred by the two different light-chain loci.
d. that surrogate light-chain transcription cannot compete with and transcription and
enables B-cell development.
e. all of the above.
6–12
Which of the following is correctly matched? (Select all that apply.)
a. Early pro-B cell: VDJ rearranged
b. Pre-B-cell receptor: VpreB5/ heavy chain
c. Mature B cell: IgM plus IgD
d. Small pre-B cell: VJ rearranged
e. Immature B cell: heavy chain plus or light chain on surface.
6–13
Large pre-B cells undergo clonal expansion before the rearrangement of light-chain loci. Which
of the following are beneficial consequences of clonal expansion? (Select all that apply.)
a. Autoreactive B cells are eliminated before the expenditure of energy needed to rearrange
a functional light-chain gene.
b. The energy used to make a functional heavy chain is not wasted as a result of the inability
to produce a functional light chain.
c. RAG gene expression is decreased, which in turn signals light-chain rearrangement.
d. A diverse population of immature B cells expressing the same \mu chain but a distinct
light chain is generated.
e. Approximately 85% of small pre-B cells will progress to the immature B-cell stage.
6–14
When expression of _______ is turned off in small pre-B cells, the result is the presence of P
nucleotides but the absence of N nucleotides in around 50% of light-chain genes.
a. Kit
b. CD19
c. TdT
d. Pax-5
e. RAG-1 and RAG-2.
6–15
A defect in which of the following proteins blocks B-cell development at the pre-B-cell stage,
resulting in almost no circulating antibodies in individuals with this defect?
a. IL-7 receptor
b. terminal deoxynucleotidyltransferase (TdT)
c. Pax-5
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d. Bruton’s tyrosine kinase (Btk)
e. CD19.
6–16
The proto-oncogene _______ is associated with the development of Burkitt’s lymphoma.
a. BCL2
b. MYC
c. CD5
d. CD19
e. Btk.
6–17
Which of the following characterizes the B-1 cells that develop prenatally?
a. They lack N nucleotides.
b. They possess polyspecificity for bacterial polysaccharide antigens.
c. They arise early in embryonic development preceding the development of the majority
subset of B cells.
d. They have little or no IgD on the cell surface.
e. All of the above.
6–18
Explain how B cells undergo the process of negative selection and indicate at which stage of
development and at which location these events occur.
6–19
What is the fate of an immature B cell that encounters and has specificity for self antigen?
a. If further heavy-chain and light-chain gene rearrangements are possible, it undergoes
apoptosis.
b. Somatic hypermutation.
c. Decrease in production of IgD.
d. Continued rearrangement of heavy-chain genes.
e. Continued rearrangement of light-chain genes.
6–20
_______ involves successive rearrangement at the light-chain loci when reactivity to self antigen
occurs during B-cell development.
a. Receptor editing
b. Somatic hypermutation
c. Chromosomal translocation
d. Clonal deletion
e. Anergy.
6–21
Which of the following pertains to the fate of immature B cells which have specificity for
univalent self antigens? (Select all that apply.)
a. The cells acquire a state of unresponsiveness called anergy.
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b. IgD is retained in the cytosol.
c. IgD on the cell surface fails to activate the B cell when bound to self antigen.
d. The cells have a much longer life-span than mature B cells.
e. The cells die by apoptosis.
6–22
The circulatory route through a lymphoid tissue for both immature B cells and mature B cells
that do not encounter specific antigen is
a. bloodstream → HEV of lymphoid cortex → primary lymphoid follicle → efferent
lymphatic vessel
b. afferent lymphatic vessel → primary lymphoid follicle → HEV of lymphoid cortex →
efferent lymphatic vessel
c. afferent lymphatic vessel → medullary cords → primary lymphoid follicle → efferent
lymphatic vessel
d. primary lymphoid follicle → HEV of lymphoid cortex → afferent lymphatic vessel →
efferent lymphatic vessel
e. bloodstream → afferent lymphatic vessel → HEV of lymphoid cortex → efferent
lymphatic vessel.
6–23
A. Identify properties that are shared by anergic B cells and plasma cells.
B. What key property is different?
6–24
Indicate which of the following statements concerning memory B cells are true (T) and which
are false (F):
___ a. Memory B cells are derived from germinal center B cells as immune responses subside.
___ b. Memory B cells have long life-spans.
___ c. Memory B cells possess high-affinity antigen receptors as a consequence of affinity
maturation.
___ d. Memory B cells have more stringent requirements for activation than naive B cells do.
___ e. Memory B cells express only IgM and retain the capacity to switch to the most beneficial
isotype during secondary responses.
6–25
Multiple myeloma involves the unregulated proliferation of an antibody-producing plasma cell
(myeloma cell) independently of antigen stimulation or T-cell help. Myeloma cells populate
multiple sites in the bone marrow, where they produce immense quantities of monoclonal
immunoglobulin as well as suppressing normal marrow function. Myeloma cells also synthesize
and secrete excessive amounts of free light chains (known as Bence-Jones protein), which,
because of their low molecular weight (~25 kDa) are excreted as free light chains in the urine.
In a given patient the free light chains are both monoclonal and all are of either the or the
type.
A. Explain both of these observations.
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B. Why do you think patients with multiple myeloma are more susceptible than normal to
pyogenic infections, such as pneumonia caused by Streptococcus pneumoniae or
Haemophilus influenzae?
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Answers
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