Deck 6: The Development of B Lymphocytes

Question 1

consequence of allelic exclusion at the immunoglobulin loci ensures that _____.(Select all that apply.)

A)B-cell receptors have a low-avidity binding
B)B cells express antigen receptors of a single specificity
C)hybrid immunoglobulins are formed
D)all functional copies of a gene are expressed
E)homogeneous B-cell receptors bind more effectively to antigen.

Answer 1

B,E

Question 2

Describe the six functionally distinct phases of B-cell development.

Answer 2

1)Repertoire assembly: Bone marrow expression of diverse B-cell receptors. (2)Negative selection: Modification,elimination or inactivation of autoreactive B cells. (3)Positive selection: Selection of a small subset of immature B cells to become mature B cells in secondary lymphoid organs. (4)Searching for infection: Patrolling for infectious material by recirculating continuously between lymph,blood and secondary lymphoid organ compartments. (5)Finding infection: B cells become activated by antigen in secondary lymphoid tissues and then undergo clonal expansion. (6)Attacking infection: B cells differentiate into plasma cells and memory cells in secondary lymphoid tissues.

Question 3

Which of the following is characteristic of a large pre-B cell?

A)VDJ is successfully rearranged and μ heavy chain is made.
B)V-J is rearranging at the light-chain locus.
C)μ heavy chain and λ or κ 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.

Answer 3

A

Question 4

Discuss the importance of the bone marrow stroma for B-cell development.
B.What would be the effect of anti-IL-7 antibodies on the development of B cells in the bone marrow,and at which stage would development be impaired? Explain your answer.

Question 5

Large pre-B cells are characterized by which of the following?

A)They do not express CD19 at the cell surface.
B)Rearrangement of light-chain genes commences.
C)Nonproductive rearrangement of both heavy-chain loci has already occurred.
D)Allelic exclusion of the immunoglobulin light-chain loci has already occurred.
E)μ is assembled with VpreBλ5.

Question 6

expression of _______ is turned off in small pre-B cells,the result is the presence of P nucleotides but an 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.

Question 7

Which of the following statements is correct?

A)The κ light-chain genes rearrange before the heavy-chain genes.
B)The κ light-chain genes rearrange before the λ light-chain genes.
C)The λ light-chain genes rearrange before the heavy-chain genes.
D)The λ light-chain genes rearrange before the κ light-chain genes.
E)The μ heavy-chain genes rearrange first and then the λ light-chain genes rearrange.

Question 8

Which of the following would occur after the production of a functional μ chain as a pre-B-cell receptor?

A)RAG proteins are degraded.
B)The chromatin structure of the heavy-chain locus is reorganized to prevent gene rearrangement.
C)Transcription of the RAG1 and RAG2 genes ceases.
D)There is allelic exclusion of a second μ chain.
E)All of the above would occur.

Question 9

Immature B cells develop into B cells in the

A)subendosteum
B)bone marrow
C)thymus
D)blood
E)secondary lymphoid organs.

Question 10

What are the two main checkpoints of B-cell development in the bone marrow?
B.What is the fate of developing B cells that produce (i)functional or (ii)nonfunctional heavy and light chains?
C.Explain how these two checkpoints correlate with the process of allelic exclusion that ensures that only one heavy-chain locus and one light-chain locus produce functional gene products.

Question 11

You are going to use flow cytometry to determine the proportion of developing B cells in the bone marrow that are immature, anergic, or mature. You have three monoclonal antibodies specific for three different B-cell surface proteins. The first has specificity for the cell-surface protein CD19, which is expressed by all developing and mature B cells; the second is specific for the Fc region of IgD; and the third is specific for the Fc region of IgM. The antibodies are conjugated to three different fluorescent tags that can be detected and distinguished by the flow cytometer.
A. Use histograms to show your analysis of CD19-positive cells and indicate which part of your histogram you would gate to analyze IgM and IgD expression. Indicate the gated population with an arrow.
B. Using a two-dimensional dot plot, compare the expression of IgD and IgM of these gated cells, and say which of these populations represents (i) immature B cells, (ii) mature B cells, and (iii) anergic B cells.

Question 12

Which of the following is not paired with its correct complement?

A)N nucleotides: more abundant in rearranged heavy-chain genes than in rearranged light-chain genes
B)second checkpoint in B-cell development: assembly of a functional B-cell receptor
C)receptor editing: exchange of light chain for one that is not self-reactive
D)first checkpoint in B-cell development: selection by the pre-B-cell receptor
E)large pre-B-cell stage: constitutive expression of RAG-1 and RAG-2 proteins.

Question 13

hematopoietic stem cells express

A)CD34
B)CD127
C)CD19
D)VpreBλ5
E)Pax-5

Question 14

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
D)Bruton's tyrosine kinase (Btk)
E)CD19.

Question 15

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 is generated that express the same μ chain but a distinct light chain.
E)Approximately 85% of small pre-B cells will progress to the immature B-cell stage.

Question 16

latest stages of late pro-B-cell development are recognized by the association of a surrogate light chain with a μ chain.The surrogate light chain is composed of

A)E2A and EFB
B)Igα and Igβ
C)VpreB and λ5
D)RAG-1 and RAG-2
E)Pax-5 and CD19.

Question 17

Which of the following is correctly matched? (Select all that apply.)

A)early pro-B cell: VDJ rearranged
B)pre-B-cell receptor: VpreBλ5/μu heavy chain
C)mature B cell: IgM plus IgD
D)small pre-B cell: VJ rearranged
E)immature B cell: μ heavy chain plus λ or κ light chain on surface.

Question 18

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).

Question 19

would be the consequence if terminal deoxynucleotidyl transferase (TdT)were expressed throughout the whole of small pre-B-cell development?

Question 20

important advantage of having two gene loci (κ and λ)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 κ and λ transcription and enables B-cell development.
E)all of the above.

Question 21

Individuals who fail to express functional Bruton's tyrosine kinase exhibit all of the following characteristics except

A)B-cell development is blocked at the immature B-cell stage.
B)They are usually male because the Btk gene is on the X chromosome.
C)They suffer from an immune deficiency known as X-linked agammaglobulinemia (XLA).
D)Recurrent infections with extracellular bacteria are common.
E)They benefit from treatment with immunoglobulin infusions.

Question 22

Negative selection of developing B cells ensures that

A)there is not an overabundance of circulating B cells that would compete with other important cell types in the circulation
B)only antigen-activated B cells leave the bone marrow
C)clonal expansion of B cells does not occur in the absence of infection
D)B-cell receptors that bind to normal constituents of the body do not emerge
E)B cells do not leave secondary lymphoid tissues.

Question 23

Which of the following statements about the IgD made by B cells of upper respiratory mucosa is not true?

A)These antibodies bind to airborne bacteria such as Haemophilus influenzae.
B)λ light chains are used almost exclusively by these IgD antibodies.
C)Two-thirds of these IgD antibodies possess κ light chains.
D)These IgD antibodies recruit basophils and induce the secretion of antibacterial peptides.

Question 24

Which of the following is a characteristic of B-2 cells?

A)They are sometimes referred to as CD5 B cells.
B)They comprise only 5% of the B-cell repertoire.
C)In adults,they are renewed by cell division in the peripheral circulation.
D)They are located primarily in secondary lymphoid organs.
E)They are not dependent on T helper cells for activation.

Question 25

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 μ 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
E)to ensure that antibodies are secreted and not membrane-bound.

Question 26

Explain how B cells undergo the process of negative selection and indicate at which stage of development and at which location these events occur.

Question 27

Immunological tolerance in the B-cell repertoire is called _______ tolerance when it develops in primary lymphoid organs,and _______ tolerance when it is induced outside the bone marrow.

A)primary; secondary
B)apoptotic; anergic
C)stromal; follicular
D)receptor-mediated; systemic
E)central; peripheral.

Question 28

proto-oncogene _______ is associated with the development of Burkitt's lymphoma.

A)BCL-2
B)Myc
C)CD5
D)CD19
E)BTK.

Question 29

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.

Question 30

is the role of primary lymphoid follicles in eliminating B cells that have antigen receptors specific for soluble self antigen?

Question 31

Identify the mismatched pair of chemokine and the cells that secrete it.

A)CCL19: lymph-node dendritic cells
B)CXCL13: follicular dendritic cells
C)CCL21: stromal cells of secondary lymphoid tissues
D)All of the above are correctly matched.

Question 32

developing B cell unable to generate a productive rearrangement on any of the four light-chain loci will undergo

A)self-renewal
B)apoptosis
C)allelic exclusion
D)malignant transformation
E)differentiation into a B-1 cell.

Question 33

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.

Question 34

Receptor editing occurs _____.(Select all that apply.)

A)in the bone marrow
B)after encounter with foreign antigen in secondary lymphoid organs
C)in mature B cells
D)to establish self-tolerance of the B-cell repertoire
E)to express an excess of IgM over IgD on the surface of mature B cells.

Question 35

plasma cell is characterized by which of the following features? (Select all that apply.)

A)It differentiates in the medulla of lymph nodes and the bone marrow.
B)It dedicates 10-20% of total protein synthesis to antibody production.
C)Levels of MHC class II molecules are elevated.
D)It undergoes extensive proliferation in germinal centers.
E)It produces secreted immunoglobulin instead of the membrane-bound form.

Question 36

Explain why immunological memory is important in acquired immunity.
B.Describe how immunoglobulin expressed during a primary immune response differs qualitatively and quantitatively from the immunoglobulin expressed during a secondary immune response.

Question 37

Which of the following pertains to the fate of immature B cells that have specificity for univalent self antigens? (Select all that apply.)

A)The cells acquire a state of unresponsiveness called anergy.
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.

Question 38

Which of the following is true of centrocytes? (Select all that apply.)

A)Somatic hypermutation has occurred.
B)They are large proliferating cells.
C)Isotype switching is complete.
D)They produce secreted forms of immunoglobulins.
E)They lack MHC class II molecules on the cell surface.

Question 39

of the following are associated with the development of Burkitt's lymphoma except

A)The expression of Myc protein is perturbed.
B)A chromosomal translocation involving a proto-oncogene and an immunoglobulin gene occurs.
C)Overproduction of the Bcl-2 protein prolongs the lifetime of B-lineage cells.
D)Cell division restraints on mutated B cells are lifted.
E)In addition to a chromosomal translocation event,mutations elsewhere in the genome are usually involved.

Question 41

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 κ or the λ type.
A.Explain both of these observations.
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?
ANSWERS

Question 42

Hinda Mundy,26 years old,grew concerned when a lump appeared in her lower neck and she had pain in her chest and a dry cough.She also told her physician that she had experienced fatigue,night sweats,unintentional weight loss,pruritis (dry,itchy skin),and intermittent fevers over the past few months.Immunohistological staining of a biopsy of the enlarged lymph node revealed the presence of large multinucleated Reed-Sternberg cells.Polymerase chain reaction (PCR)tests confirmed immunoglobulin gene rearrangements; however,B-cell antigen expression was absent.Hinda entered complete remission after treatment with four cycles of chemotherapy combined with radiotherapy.These symptoms and treatment are most consistent with a diagnosis of
a.Hodgkin's lymphoma
b.multiple myeloma
c.acute lymphoblastic leukemia (ALL)
d.Waldenström's magroglobulinemia
e.chronic lymphocytic leukemia (CLL).

Question 43

Identify properties that are shared by anergic B cells and plasma cells.
B.What key property is different?

Question 44

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.

Question 45

Give three properties that distinguish B-1 cells from B-2 cells.
B.Do you think that B-1 cells should be categorized as participants in innate immune responses or in acquired immune responses? Explain your rationale.