B Cell Development

Question 1

B cell differentiation begins with the expression of
a. membrane m chain + surrogate L chain.
b. membrane IgD.
c. Membrane IgM.
d. germline IgM.
e. RAG-1, RAG-2 and TdT.

Answer 1

e. RAG-1, RAG-2 and TdT.

Question 2

Bone marrow stromal cells
a. are important because they provide physical support for B cells (hence, their name from the Greek word for mattress).
b. are present only in the center of the marrow.
c. present foreign antigen to B cells to stimulate somatic hypermutation .
d. present self antigen on self MHC to B cells for negative selection.
e. secrete cytokines such as IL-7 that signal developing B cells to divide and differentiate.

Answer 2

e. secrete cytokines such as IL-7 that signal developing B cells to divide and differentiate.

Question 3

Cell adhesion molecules (CAMs)
a. are found only on bone marrow stromal cells.
b. are specific receptors for cytokines that promote cell-cell binding.
c. function primarily to hold developing B cells in one location until they are fully developed.
d. signal developing B cells to divide and differentiate.
e. signal developing B cells to die because they have bound self.

Answer 3

d. signal developing B cells to divide and differentiate.

Question 4

The developmental step that commits a cell to the B lineage is
a. expression of both membrane IgM and IgD.
b. expression of membrane m chain.
c. expression of recombinase enzymes.
d. joining of a VH gene segment to a DH gene segment.
e. joining of a DH gene segment to a JH gene segment

Answer 4

e. joining of a DH gene segment to a JH gene segment

Question 5

Which statement about B cell development is FALSE?
a. Cells which fail to synthesize and express m chains usually die.
b. Each DNA joining event in Ig genes has a 67% probability of resulting in a nonproductive rearrangement.
c. The earliest developing B cell which could be stained with FITC-anti-m chain would be a pro B cell.
d. The earliest developing B cell which could be stained with FITC-anti- k chain would be an immature B cell.
e. The enzyme which can add nucleotides not encoded in the DNA to Ig genes during recombination is TdT.

Answer 5

c. The earliest developing B cell which could be stained with FITC-anti-m chain would be a pro B cell.

Question 6

Once H chain genes have been productively rearranged and expressed on the pre-B cell membrane, the next event to occur in the cell is
a. death of cells binding self antigen.
b. expression of membrane IgD.
c. expression of membrane of IgM.
d. proliferation of the pre-B cells.
e. somatic recombination of light chain genes.

Answer 6

d. proliferation of the pre-B cells.

Question 7

In a productive rearrangement of Ig DNA, what is produced must be
a. a functional membrane Ig protein chain.
b. a loop of DNA that is then removed.
c. an mRNA for H or L chain.
d. a shorter piece of DNA.
e. successful antibody secretion in response to antigen.

Answer 7

a. a functional membrane Ig protein chain.

Question 8

Proliferation of large pre-B cells
a. is part of clonal selection.
b. makes the pre-B cells more susceptible to apoptosis following self antigen binding
c. results in production of many B cells with the same antigen specificity.
d. results in the production of many B cells with the same VH chain but different antigen specificities due to different VL regions.
e. requires the presence of RAG-1 and RAG-2.

Answer 8

d. results in the production of many B cells with the same VH chain but different antigen specificities due to different VL regions.

Question 9

Which of the following statements is TRUE?
a. Isotypic exclusion on individual B cells pertains to expression of a single heavy chain isotype on each mature naive B cell.
b. Pre-B cells must receive a signal from specific antigen binding to pre-B receptor before they can proceed to the next stage in development.
c. Membrane m chain is always expressed with Iga and Igb
d. Membrane m chain is always expressed with VpreB and l5.
e. Transgenic mice for recombined H and L immunoglobulin genes have germline H and L genes in non-B cells.

Answer 9

c. Membrane m chain is always expressed with Iga and Igb

Question 10

Light chain rescue
a. allows self-specific B cells to repeat somatic recombination of light chain gene segments.
b. is a signal received through binding to the surrogate light chain that rescues the developing B cell from death.
c. results from multiple V-J joining events on a single chromosome until productive rearrangement of light chain occurs or all J segments have been recombined.
d. signals the developing B cell through IgaIgb to begin recombination of light chain gene segments.
e. None of the above is true.

Answer 10

c. results from multiple V-J joining events on a single chromosome until productive rearrangement of light chain occurs or all J segments have been recombined.

Question 11

Regulatory nucleotide sequences in the DNA that control Ig protein synthesis are
a. inducers and promoters.
b. initiation sites and enhancers.
c. promoters and enhancers.
d. promoters and switch regions.
e. recombination signal sequences and promoters.

Answer 11

c. promoters and enhancers.

Question 12

Transgenic mice for BCR
a. are given a completely new set of Ig genes.
b. express the recombined H chain gene on every cell in the body.
c. have germline H chain gene segments in all their cells except B cells.
d. suppress their own H chain V-D-J recombination if they have been given a recombined H chain gene.
e. synthesize Ig with the same amount of diversity as non-transgenic mice.

Answer 12

d. suppress their own H chain V-D-J recombination if they have been given a recombined H chain gene.

Question 13

If the Ig V regions encoded in the transgenes were specific for self MHC, the transgenic mice
a. might be able to produce low numbers of non-self-specific B cells through receptor editing.
b. would produce normal numbers of B cells because MHC is not expressed in the marrow.
c. would die of autoimmunity.
d. would fail to produce any B cells.
e. would not die of autoimmunity because only T cells bind MHC.

Answer 13

a. might be able to produce low numbers of non-self-specific B cells through receptor editing.

Question 14

In general, a knock-out mouse
a. does not show allelic exclusion of Ig.
b. has a mutant TdT that removes (knocks out) N nucleotides instead of inserting them during somatic recombination.
c. has no Ig gene segments.
d. has a normal gene replaced with a nonfunctional gene for the same protein.
e. is often used to produce monoclonal antibody.

Answer 14

d. has a normal gene replaced with a nonfunctional gene for the same protein.

Question 15

Knock-out mice which have m gene segments from which the membrane domain has been removed
a. cannot synthesize any m chain.
b. can splice the Cm segments to the membrane segment for d and express normal amounts of membrane m chain.
c. have normal pro-B cells but no later stages of developing or mature B cells.
d. have normal pro-B cells and pre-B cells but no mature B cells.
e. have no cells with rearranged Ig genes.

Answer 15

c. have normal pro-B cells but no later stages of developing or mature B cells.

Question 16

B cells which express Iga with a truncated cytoplasmic domain (lacking the ITAMS)
a. become “stuck” in the immature B cell stage of development.
b. can express pre-B cell receptor but not proceed to divide and then recombine light chain genes.
c. develop normally since Igb has its ITAM sequences.
d. express both IgM and IgD but cannot be activated by antigen.
e. require more antigen for activation.

Answer 16

b. can express pre-B cell receptor but not proceed to divide and then recombine light chain genes.

Question 17

The ability of an individual B cell to express only one H chain allotype is called
a. allelic exclusion.
b. co-dominant expression.
c. isotypic exclusion.
d. nonproductive rearrangement.
e. survival of the fittest.

Answer 17

a. allelic exclusion.

Question 18

Once they leave the marrow, in order to survive mature naive B cells must enter the
a. circulation
b. lymph microenvironment.
c. primary lymphoid follicles.
d. secondary lymphoid follicles.
e. thymus.

Answer 18

c. primary lymphoid follicles.

Question 19

Negative selection of B cells occurs when
a. immature B cells bind self antigen and undergo apoptosis.
b. immature B cells fail to bind self MHC and die.
c. lymphoid progenitor cells become committed to becoming T cells and leave the marrow for the thymus.
d. mature B cells fail to bind antigen in the lymphoid follicles and die.
e. pre-B cells bind ligand with their pre-B receptor and stop rearranging H chain genes.

Answer 19

a. immature B cells bind self antigen and undergo apoptosis.

Question 20

A mature lymphocyte which has specific antigen receptors but cannot respond to that antigen is called
a. anergic.
b. apoptotic.
c. deleted.
d. lazy.
e. memory.

Answer 20

a. anergic.

Question 21

Immature B cells which bind soluble self antigen
a. become apoptotic.
b. escape clonal deletion and can potentially cause autoimmune disease in adults.
c. go on to express normal levels of IgM and IgD but cannot respond to self antigen.
d. undergo clonal deletion in the bone marrow.
e. usually cannot enter the primary lymphoid follicles and soon die in the periphery.

Answer 21

e. usually cannot enter the primary lymphoid follicles and soon die in the periphery.

Question 22

Immature B cells from inbred mouse strain q (expressing the q allele of every MHC molecule: Dq, Kq, Lq, IAq, and IEq) which also express transgenic H and L chains specific for H-2 IAs (the s allele of Class II MHC IA) will undergo clonal deletion when
a. exposed to macrophages from an “s” strain mouse (expressing the “s” allele of every MHC molecule).
b. exposed to T cells from an s strain mouse.
c. exposed to their own macrophages.
d. exposed to their own T cells.
e. Both 1 and 2 are correct.

Answer 22

e. Both 1 and 2 are correct.

Question 23

Chickens have very few functional V, D, and J gene segments and therefore
a. are very susceptible to disease.
b. have many self-specific lymphocytes and usually die of autoimmune disease.
c. insert diverse sequences from VH pseudogenes into their H chains while B cells are immature.
d. make mature B cells which are all specific for the same antigen.
e. use gene conversion to introduce diversity into Ig gene sequences as B cells divide in response to foreign antigen.

Answer 23

c. insert diverse sequences from VH pseudogenes into their H chains while B cells are immature.

Question 24

The B cells with the longest life span are the
a. anergized B cells.
b. immature B cells.
c. mature naive B cells.
d. memory cells.
e. plasma cells.

Answer 24

d. memory cells.

Question 25

Receptor editing
a. allows self-specific B cells to repeat somatic recombination.
b. is responsible for allelic exclusion of Ig on individual B cells.
c. kills self-specific B cells before they leave the marrow.
d. occurs during the small pro-B cell stage of development.
e. occurs only for light chains of self-specific B cells.

Answer 25

a. allows self-specific B cells to repeat somatic recombination.

Question 26

B-1 B cells are more ________ than conventional B (B-2) cells.
a. antigen-specific
b. high affinity
c. likely to be protein-specific
d. numerous in adults
e. polyreactive

Answer 26

e. polyreactive

Question 27

The antibody secreted by B-1 B cells often
a. binds common bacterial carbohydrates.
b. has a high affinity for antigen.
c. is IgG.
d. neutralizes common viral receptor proteins.
e. neutralizes self antigens.

Answer 27

a. binds common bacterial carbohydrates.

Question 28

As cells become mature naive B cells, they
a. become more antigen-independent.
b. leave the marrow and never return.
c. stay in one location and wait for antigen and T cells to come to them.
d. stay in the same locations as T cell to be able to receive helper signals.
e. use CAMs to enter the appropriate lymphoid organ locations.

Answer 28

e. use CAMs to enter the appropriate lymphoid organ locations.

Question 29

A germinal center is where B cells
a. become mature.
b. divide in response to antigen.
c. first bind antigen.
d. secrete antibody.
e. undergo somatic recombination.

Answer 29

b. divide in response to antigen.

Question 30

If you wanted to check for the presence of memory B cells from your vaccine subjects by taking some of their B cells and re-stimulating them in vitro (outside the body) with antigen, the best place to get some memory cells would be from
a. blood.
b. bone marrow.
c. lymph nodes.
d. spleen.
e. tonsils.

Answer 30

a. blood.

Question 31

Multiple myeloma is a cancer which has arisen from a
a. B-1 B cell.
b. lymphoid progenitor.
c. mature B cell.
d. plasma cell.
e. pre-B cell.

Answer 31

d. plasma cell.

Question 32

If a B cell tumor is monoclonal, it can be differentiated from normal B cells of the same person by its unique membrane Ig
a. allotype.
b. H chain.
c. idiotype.
d. isotype.
e. L chain.

Answer 32

c. idiotype.

Question 33

An oncogene is a
a. gene for a virus protein that causes cancer.
b. gene for tumor antigens on B cells.
c. mutated gene that causes cancer.
d. normal gene that can cause cancer if its normal function is disrupted.
e. translocated Ig gene.

Answer 33

d. normal gene that can cause cancer if its normal function is disrupted.