Question 1

Which of the following is NOT a property of the V(D)J recombinase?&#10;A) Recognizes specific DNA sequences flanking gene segments in the antigen receptor gene loci&#10;B) Introduces double-stranded nicks in the DNA between recombination signal sequences and the adjacent V, D, or J coding sequences&#10;C) Promotes joining V-to-J, D-to-J, and V-to-D&#10;D) Repairs double-stranded DNA breaks&#10;E) Splices out intronic sequences from primary RNA transcripts

Accepted Answer

The V(D)J recombinase is an enzyme complex that includes the lymphocyte-specific RAG-1 and RAG-2 proteins, as well as other more widely expressed DNA repair enzymes
This recombinase acts on DNA in the antigen receptor gene loci but does not mediate RNA splicing
The RAG-1 protein binds to recombination signal sequences (RSSs), cleaves the adjacent DNA, and promotes alignment of the different segments to be joined
Other enzymes in the complex ligate the cleaved DNA ends to form the functional gene, encoding a chain of the antigen receptor.

Question 2

Which of the following statements about negative selection during lymphocyte development is most accurate?&#10;A) The mechanism of negative selection is the death of cells whose antigen receptors are not stimulated by self antigens.&#10;B) The mechanism of negative selection is apoptosis actively induced by antigen-receptor recognition of self antigens.&#10;C) Negative selection ensures a self MHC restricted repertoire of T lymphocytes.&#10;D) Negative selection occurs only in T cell maturation and not in B cell maturation.&#10;E) The major mechanism of negative selection is inhibition of antigen receptor expression.

Accepted Answer

Negative selection is a mechanism that promotes a self-tolerant lymphocyte repertoire for both B and T cells
It occurs in the generative lymphoid organs (bone marrow and thymus) when developing lymphocytes express antigen receptors that bind strongly to self antigens
The major mechanism is actively induced apoptosis; immature lymphocytes that receive strong antigen receptor-mediated signals are particularly susceptible to death by apoptosis
Positive selection in the thymus promotes a self-MHC-restricted T cell repertoire.

Question 3

The figure depicts the germline organization of gene segments of the Ig heavy chain locus on chromosome 14.
Choose the lettered label on the figure (A-E) that best matches the description in questions .

A segment that encodes Ig-like domains that form part of the antigen-binding region of an Ig molecule

Accepted Answer

A&#10;One variable (V) gene segment, from as many as 45 possible V gene segments, is used in each functional Ig heavy chain gene&#10;This V gene segment encodes an Ig domain that includes complementarity-determining regions (CDRs) 1 and 2 of the antigen-binding region of the heavy chain.

Question 4

The figure depicts the germline organization of gene segments of the Ig heavy chain locus on chromosome 14.
Choose the lettered label on the figure (A-E) that best matches the description in questions .

Encodes the isotype of antibodies made by naive B cells

Accepted Answer

The answer of The figure depicts the germline organization of...

Question 5

Which of the following is NOT an example of a checkpoint in lymphocyte maturation that contributes to the selective maturation of cells with useful antigen receptors?&#10;A) B cell precursors that cannot express Ig g heavy chains die by apoptosis.&#10;B) T cell precursors that cannot express TCR b chains die by apoptosis.&#10;C) Immature B cells that bind to self antigen with high affinity die by apoptosis.&#10;D) Developing T cells that fail to express TCR a chains die by apoptosis.&#10;E) Developing T cells that recognize self major histocompatibility complex (MHC) molecules with high affinity die by apoptosis.

Accepted Answer

B cell precursors must express Ig m heavy chains (not Ig g heavy chains) to survive
The m chains associate with surrogate light chains in pre-B cells, which allows for the generation of survival signals
Otherwise, the cells die by a default apoptotic pathway
A similar checkpoint exists in T cell precursors, which must express TCR b chains that associate with pre-Ta chains to avoid apoptotic death
Developing T cells must progress to express TCR a chains and form ab TCRs to be positively selected and continue to survive
Both immature B cells and developing T cells will undergo apoptosis if they express high-affinity receptors that bind to self antigens
In the case of developing T cells, high-affinity binding to self MHC will lead to apoptotic death.

Question 6

Matching&#10;The block in the stage of lymphocyte development described in questions , will be caused by a mutation in which of the genes listed (A-F)?&#10;Pro-B cell to pre-B cell&#10;A) &#10;B) &#10;C) &#10;D) &#10;E) &#10;F)

Accepted Answer

Pro-B to pre-B transition requires expression of Ig m heavy chains
Functional m heavy chain genes are formed by RAG-1- and RAG-2-dependent VDJ recombination.

Question 7

Matching&#10;The block in the stage of lymphocyte development described in questions , will be caused by a mutation in which of the genes listed (A-F)?&#10;Stem cell to committed B or T lineage precursor&#10;A) &#10;B) &#10;C) &#10;D) &#10;E) &#10;F)

Accepted Answer

Ikaros is a transcription factor required for transition of a pluripotential stem cell to a cell committed to either B or T lymphocyte lineages.

Question 8

The figure depicts the germline organization of gene segments of the Ig heavy chain locus on chromosome 14.
Choose the lettered label on the figure (A-E) that best matches the description in questions .

A type of gene segment involved in somatic recombination events in Ig heavy chain and light chain as well as TCR a and b chain gene loci

Accepted Answer

The answer of The figure depicts the germline organization of...

Question 9

The figure depicts the germline organization of gene segments of the Ig heavy chain locus on chromosome 14.
Choose the lettered label on the figure (A-E) that best matches the description in questions .

A segment that encodes Ig-like domains that form part of the antigen-binding region of an Ig molecule

A
One variable (V) gene segment, from as many as 45 possible V gene segments, is used in each functional Ig heavy chain gene
This V gene segment encodes an Ig domain that includes complementarity-determining regions (CDRs) 1 and 2 of the antigen-binding region of the heavy chain.

Accepted Answer

The answer of The figure depicts the germline organization of...

Question 10

Which of the following is NOT a required step in B and T lymphocyte maturation?&#10;A) Proliferative expansion of precursor cells&#10;B) Cell surface expression of complete antigen receptor complexes&#10;C) Positive selection&#10;D) Activation of precursors by foreign antigens&#10;E) Pre-antigen receptor expression

Accepted Answer

Foreign antigens are not likely to be present in the generative lymphoid organs where lymphocytes mature and thus are not involved in the process
Both B cell and T cell maturation include sequential steps, including cytokine-induced proliferation and expansion of immature precursors, somatic recombination of Ig heavy chain or T cell receptor (TCR) b chain genes, expression of m heavy chain or TCR b chain with a surrogate nonvariable partner to form a pre-Ig or pre-TCR, somatic recombination of Ig light chain or TCR a chain genes, expression of complete antigen receptors and associated signaling molecules, and positive selection by recognition of self antigens.

Question 11

Matching&#10;The block in the stage of lymphocyte development described in questions , will be caused by a mutation in which of the genes listed (A-F)?&#10;CD4+CD8+ thymocyte to single positive CD8+ thymocyte&#10;A) &#10;B) &#10;C) &#10;D) &#10;E) &#10;F)

Accepted Answer

The answer of Matching&#10;The block in the stage of lymphocyte...

Deck 17: Lymphocyte Maturation and Expression of Antigen Receptor Genes