Podcast
Questions and Answers
Which enzyme catalyzes the random addition of nucleotides that are not part of germline genes to the junctions between V and D segments and D and J segments, forming so-called N regions?
Which enzyme catalyzes the random addition of nucleotides that are not part of germline genes to the junctions between V and D segments and D and J segments, forming so-called N regions?
- Terminal deoxyribonucleotidyl
- ARTEMIS
- TdT (correct)
- Exonucleases
What is almost unlimited due to changes in nucleotide sequences introduced at the junctions of the recombining V, D, and J gene segments?
What is almost unlimited due to changes in nucleotide sequences introduced at the junctions of the recombining V, D, and J gene segments?
- Exonucleases
- Combinatorial diversity
- ARTEMIS
- Junctional diversity (correct)
Which enzyme cuts the hairpin loops asymmetrically during the DNA repair process, forming overhanging DNA sequences?
Which enzyme cuts the hairpin loops asymmetrically during the DNA repair process, forming overhanging DNA sequences?
- DNA polymerase
- Exonucleases
- ARTEMIS (correct)
- TdT
What mechanism generates more sequences than are present in the germline genes by creating new coding sequences not in the germline DNA?
What mechanism generates more sequences than are present in the germline genes by creating new coding sequences not in the germline DNA?
What is the function of pre-BCR in B cell maturation?
What is the function of pre-BCR in B cell maturation?
What happens to B cells that fail to make productive Ig H chain rearrangement?
What happens to B cells that fail to make productive Ig H chain rearrangement?
Which protein is associated with pre-B cells and forms the pre-B cell receptor (pre-BCR)?
Which protein is associated with pre-B cells and forms the pre-B cell receptor (pre-BCR)?
What is the consequence of pre-BCR signaling on the second chromosome?
What is the consequence of pre-BCR signaling on the second chromosome?
What results from mutations in BTK, a downstream tyrosine kinase in pre-BCR signaling pathway?
What results from mutations in BTK, a downstream tyrosine kinase in pre-BCR signaling pathway?
What signals the BCR complex provides for immature B cells?
What signals the BCR complex provides for immature B cells?
Which signals shut off further recombination, resulting in each B cell producing one κ or λ light chain?
Which signals shut off further recombination, resulting in each B cell producing one κ or λ light chain?
Where do B cells mature further and coexpress IgD and IgM?
Where do B cells mature further and coexpress IgD and IgM?
On what basis are developing B cells positively selected?
On what basis are developing B cells positively selected?
Where does negative selection occur during the development of B cells?
Where does negative selection occur during the development of B cells?
What mediates the Ig gene recombination in developing B cells?
What mediates the Ig gene recombination in developing B cells?
What are the three main subsets of mature B cells?
What are the three main subsets of mature B cells?
What is the first TCR β chain expressed during T cell maturation?
What is the first TCR β chain expressed during T cell maturation?
What is involved in the early steps of T cell maturation?
What is involved in the early steps of T cell maturation?
What characteristic distinguishes marginal-zone B cells from other subsets of mature B cells?
What characteristic distinguishes marginal-zone B cells from other subsets of mature B cells?
What type of T cells develop from the TCR β chain-expressing cells?
What type of T cells develop from the TCR β chain-expressing cells?
What is the process called when a V gene recombines directly with a J gene segment in loci lacking D segments?
What is the process called when a V gene recombines directly with a J gene segment in loci lacking D segments?
What maximizes the variability in the antigen-recognizing portions of antibodies and TCRs, specifically in the CDR3 loop?
What maximizes the variability in the antigen-recognizing portions of antibodies and TCRs, specifically in the CDR3 loop?
What is the result of the recombination of Ig heavy chain genes?
What is the result of the recombination of Ig heavy chain genes?
Which gene recombination event involves deletion of intervening gene segments?
Which gene recombination event involves deletion of intervening gene segments?
What is the process that contains checkpoints to select cells with functional receptors and eliminate cells with out-of-frame sequences?
What is the process that contains checkpoints to select cells with functional receptors and eliminate cells with out-of-frame sequences?
Which sequence lacks D segments in the recombination process of Ig light chains and TCR α and β chains?
Which sequence lacks D segments in the recombination process of Ig light chains and TCR α and β chains?
What contributes to the total possible numbers of distinct B and T cell antigen receptors?
What contributes to the total possible numbers of distinct B and T cell antigen receptors?
What is the result of splicing the VDJ complex onto the C region exons of the first heavy-chain RNA (μ)?
What is the result of splicing the VDJ complex onto the C region exons of the first heavy-chain RNA (μ)?
What differs in the nucleotide sequence of the V(D)J exons in antibody or TCR genes in one clone of lymphocytes from every other clone?
What differs in the nucleotide sequence of the V(D)J exons in antibody or TCR genes in one clone of lymphocytes from every other clone?
What does junctional diversity maximize specifically in antibodies and TCRs?
What does junctional diversity maximize specifically in antibodies and TCRs?
What is the consequence of failure in both inherited loci during VDJ recombination in pre-T cells?
What is the consequence of failure in both inherited loci during VDJ recombination in pre-T cells?
What is the outcome of successful recombination in one of the two inherited loci during VDJ recombination in pre-T cells?
What is the outcome of successful recombination in one of the two inherited loci during VDJ recombination in pre-T cells?
What do low to moderate affinity interactions during positive selection in the thymus result in?
What do low to moderate affinity interactions during positive selection in the thymus result in?
What is the fate of CD8+ T cells during positive selection in the thymus?
What is the fate of CD8+ T cells during positive selection in the thymus?
From which type of immature CD4+ T cells do regulatory T cells (Tregs) develop during negative selection?
From which type of immature CD4+ T cells do regulatory T cells (Tregs) develop during negative selection?
What mediates both positive and negative selection of T cells?
What mediates both positive and negative selection of T cells?
What determines the choice between positive and negative selection of T cells in the thymus?
What determines the choice between positive and negative selection of T cells in the thymus?
What leads to negative selection of T cells?
What leads to negative selection of T cells?
In what situation does failure of positive selection (death by neglect) occur?
In what situation does failure of positive selection (death by neglect) occur?
What is the outcome of weak recognition of rare self antigens during positive selection?
What is the outcome of weak recognition of rare self antigens during positive selection?
What is the function of CD4+ T cells during positive selection?
What is the function of CD4+ T cells during positive selection?
What is the outcome of high affinity interactions during positive selection?
What is the outcome of high affinity interactions during positive selection?
Study Notes
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B lymphocytes undergo unique maturation process in bone marrow (Fig. 4.12)
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Pro-B cells are early progenitors, undergo Ig heavy-chain gene rearrangement (D to J)
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Pre-B cells express Ig μ heavy-chain protein, associate with surrogate light chains and form pre-B cell receptor (pre-BCR)
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Pre-BCR signals promote survival and proliferation of B cells with productive Ig H chain rearrangement
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B cells that fail to make productive Ig H chain rearrangement cannot form pre-BCR and die by apoptosis
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Pre-BCR signals shut off Ig H chain rearrangement on the second chromosome, ensuring allelic exclusion
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Pre-BCR complex induces V to J rearrangement of κ light-chain gene, leading to production of κ protein and cell surface IgM
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Immunoglobulin gene expression and protein expression change throughout the maturation process
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X-linked agammaglobulinemia results from mutations in BTK, a downstream tyrosine kinase in pre-BCR signaling pathway.
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Pre-T cells undergo VDJ recombination to produce TCR β chain proteins, which form the pre-TCR complex with pre-Tα protein.
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Successful recombination in one of the two inherited loci leads to pre-TCR expression, promoting cell survival, proliferation, and α gene recombination.
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Failure in both loci results in cell death.
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Pre-TCR complex signals lead to T cell maturation and differentiation into double-positive T cells.
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Double-positive T cells undergo positive selection in the thymus based on self MHC-peptide recognition.
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Low to moderate affinity interactions result in survival and the emergence of single-positive T cells.
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CD8+ T cells become cytotoxic T lymphocytes (CTLs) and CD4+ T cells differentiate into cytokine-producing helper T cells.
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High affinity interactions during positive selection result in apoptosis to avoid autoimmune responses.
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Negative selection eliminates potentially dangerous T cells through recognition of self peptide-MHC complexes.
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Regulatory T cells (Tregs) develop from some immature CD4+ T cells with intermediate avidity during negative selection.
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Both positive and negative selection are mediated by recognition of self MHC-peptide complexes.
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The choice between positive and negative selection depends on the affinity of the TCR and the concentration of the self antigen in the thymus.
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Weak recognition of abundant self antigens leads to negative selection, while weak recognition of rare self antigens leads to positive selection and T cell maturation.
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Failure of positive selection (death by neglect) occurs in strong recognition of self antigens.
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Explore how the uniqueness of CDR3 sequences in lymphocyte clones can be utilized to differentiate between neoplastic and reactive proliferations of B and T lymphocytes. Understand how the principle of CDR3 sequence variations can be applied to define the magnitude of a...
