Lecture 21: Lymphocyte Development

What is the role of the RAG complex (RAG1, RAG2) in B cell receptor development?

What is the general structure of the heavy chain of the B cell receptor (BCR)?

What is allelic exclusion?

What is the fate of a developing B cell that fails to correctly rearrange either the heavy or light chain genes?

Which event must precede antigen receptor rearrangement during B and T cell development?

Which cytokine primarily stimulates the proliferation of lymphocyte progenitors during early B and T cell development?

Which of the following best describes the role of stromal cells in B cell development?

Which process is responsible for increasing diversity in the variable region of B cell receptors during development?

What is the correct order of heavy chain gene segment rearrangement in developing B cells?

Which of the following describes the '12/23 rule' in V(D)J recombination?

During somatic recombination, what nucleotide addition is randomly added by terminal deoxynucleotidyl transferase (TdT)?

What is the significance of mutations in the AIRE gene?

What is the initial immunoglobulin expressed by immature B cells?

What process allows for the co-expression of IgM and IgD on mature B cells?

Which of the following surface markers is associated with B cell lineage determination?

What is the role of Follicular Dendritic Cells (FDCs) in B cell development?

Why is negative selection important in B and T cell development?

In T cell development, what is the significance of double-positive (DP) cells?

What is the function of the AIRE protein in the thymus?

Which type of T cell expresses a T cell receptor composed of gamma and delta chains rather than alpha and beta chains?

What is the primary function of thymic stromal lymphopoietin (TSLP) in T cell development?

Which of the following is a possible outcome of a T cell interacting with a cortical thymic epithelial cell (cTEC)?

What is the earliest stage of T cell development in the thymus in which cells lack both CD4 and CD8 expression?

Mutations in the RAG1/2 genes can lead to which immunodeficiency?

What phenotype describes cells in Omenn syndrome?

What is the immediate consequence of successful TCR beta chain expression?

What distinguishes a pro-B cell from a stem cell during B lymphocyte development?

What cell type expresses a pre-B-cell receptor composed of rearranged heavy chains and surrogate light chains?

Once a developing B cell successfully rearranges the heavy chain, what event triggers V rearrangement?

What cell type allows immature B cells to get access to lymphoid follicles?

Transcription factors PAX5 and Notch1 are necessary for:

What processes of lymphocyte maturation occur in the central lymphoid organs?

Which cell type do T-cell precursors travel from the bone marrow to develop in?

Which of the following must occur for the B cell to rearrange V gene segments of the light chain?

Which of the following accurately describes the relationship between the light chain (LC) and heavy chain (HC) gene loci in B cells?

Which stage of T cell development is characterized by the cells expressing both CD4 and CD8?

Severe combined immunodeficiency (SCID) can result from:

What role does cellular proliferation perform in lymphocyte repertoire diversity?

During somatic recombination in B cells, which of the following accurately describes the sequence of events?

What is the consequence if a developing B cell fails to successfully rearrange the light chain genes after heavy chain rearrangement?

Which of the following is the primary function of the heptamer and nonamer sequences flanking the V, D, and J gene segments?

Which of the following mechanisms contributes to the diversity of antigen receptors during lymphocyte development?

Which of the following is the defining characteristic of a pro-B cell?

Which of the following cell types mediates negative selection in the thymus by presenting self-antigens to developing T cells?

In T cell development, what event is signaled by successful TCR beta chain rearrangement?

What distinguishes the function of cortical thymic epithelial cells (cTECs) from medullary thymic epithelial cells (mTECs) in T cell development?

Which outcome is associated with mutations causing a loss of function of the AIRE gene?

Which cell expresses a pre-B cell receptor composed of rearranged heavy chains and surrogate light chains?

What role do follicular dendritic cells (FDCs) play in B cell development within the germinal centers?

Which of the following best describes the mechanism by which co-expression of IgM and IgD is achieved in mature B cells?

Which of the following is the primary role of thymic stromal lymphopoietin (TSLP) in T cell development?

In the context of V(D)J recombination, what is the biochemical function of terminal deoxynucleotidyl transferase (TdT)?

How does the process of allelic exclusion contribute to B cell receptor (BCR) specificity?

During T cell development, what is the significance of a double-negative (DN) thymocyte?

What is the functional consequence of a mutation that disrupts the 12/23 rule in V(D)J recombination?

Severe combined immunodeficiency (SCID) can result from mutations in the IL-7 receptor. What is the mechanism that connects the loss of IL-7 signaling to SCID?

During somatic recombination, under what circumstances would an RRS with a 12 bp spacer be joined to an RRS with another 12 bp spacer?

How does the lack of thymic expression of tissue-restricted self-antigens (TRASs) influence self-tolerance?

Considering the stochastic nature of V(D)J recombination and the combinatorial diversity arising from heavy and light chain pairing, what imposed constraint is primarily responsible for ensuring that each B cell expresses a BCR of a single antigen specificity?

Given the expression of both IgM and IgD is regulated by mRNA splicing, what regulatory mechanism precisely determines the ratio of membrane-bound versus secreted forms of IgM and IgD during a B cell's transition from immature to mature?

During T cell development, positive selection in the thymic cortex is essential for ensuring MHC restriction. What specific characteristic of the TCR-MHC interaction determines whether a thymocyte receives a survival signal during positive selection?

Central tolerance in the thymus depends on medullary thymic epithelial cells (mTECs) expressing a wide array of tissue-restricted antigens (TRAs) under the control of the AIRE protein. How does the presentation of TRAs by mTECs contribute to the prevention of autoimmunity targeting highly differentiated cells?

Considering the inherent error rate of DNA polymerases during somatic hypermutation in B cells, what safeguard mechanisms are in place to prevent malignant transformation resulting from off-target mutations in proto-oncogenes or tumor suppressor genes?

Given the role of IL-7 in promoting the proliferation of early lymphocyte progenitors, how does signaling via the IL-7 receptor (IL-7R) impact the expression of genes encoding for proteins involved in V(D)J recombination?

Central tolerance induction requires both deletion of strongly autoreactive T cells and the development of regulatory T cells (Tregs). What unique property of the TCR signaling threshold in the thymus determines whether a thymocyte differentiates into a Treg rather than undergoing apoptosis?

Considering the function of terminal deoxynucleotidyl transferase (TdT) in introducing N-nucleotides during V(D)J recombination, what is the most likely consequence of TdT activity being dysregulated, leading to excessive N-nucleotide addition?

In the context of somatic hypermutation (SHM) within germinal centers, what mechanism prevents AID-mediated cytosine deamination from indiscriminately mutating the entire genome, leading to genomic instability and cellular transformation?

Considering that RAG1/2 proteins are involved in both combinatorial and junctional diversity during V(D)J recombination, what would be the most plausible mechanism by which mutations in RAG1/2 could lead to Omenn syndrome, characterized by oligoclonal T cells?

Given the importance of the 12/23 rule in V(D)J recombination, what would be the most likely consequence of a mutation that alters the spacing within a recombination signal sequence (RSS) from 12 to 23 base pairs, or vice versa?

Within the intricate choreography of T cell development, double-positive (DP) thymocytes undergo positive selection based on their TCR affinity for self-MHC molecules. What critical signaling event is triggered upon successful engagement of the TCR with self-MHC that commits the DP thymocyte to a specific T cell lineage (CD4+ or CD8+)?

Central tolerance induction relies on the ability of medullary thymic epithelial cells (mTECs) to ectopically express a vast array of tissue-restricted self-antigens (TRAs) under the control of the autoimmune regulator (AIRE) protein. What mechanism ensures that TRAs are processed and presented on both MHC class I and class II molecules to effectively screen developing T cells?

Mature B cells achieve co-expression of IgM and IgD through alternative mRNA splicing. How does the cell regulate the ratio of IgM to IgD expression to fine-tune its sensitivity to antigen stimulation?

Given the role of recombination signal sequences (RSSs) in directing V(D)J recombination, how might epigenetic modifications in the vicinity of RSSs control lineage-specific antigen receptor gene rearrangement?

During T cell development, what would be the most likely outcome if a double-positive (DP) thymocyte expresses a T cell receptor (TCR) that binds with high affinity to both MHC class I and MHC class II molecules on cortical thymic epithelial cells (cTECs)?

In the context of the development of gamma-delta (γδ) T cells, what mechanism explains their capacity to respond rapidly to stress signals and infections without prior sensitization, in contrast to the antigen-dependent activation of alpha-beta (αβ) T cells?

Given that terminal deoxynucleotidyl transferase (TdT) is primarily active during heavy chain rearrangement, how does its absence specifically impact the diversity and composition of the B cell repertoire, particularly in early B cell development?

How is the ordered rearrangement of antigen receptor genes ensured during lymphocyte development, considering that RAG1/2 proteins recognize identical recombination signal sequences (RSSs) flanking V, D, and J gene segments?

The pre-TCR signaling ensures survival and proliferation of thymocytes after successful TCR-beta chain rearrangement. What downstream signaling pathways activated by the pre-TCR are indispensable for mediating allelic exclusion of the TCR-beta locus?

To what extent does differential expression of transcription factors influence the commitment of multipotent progenitors toward either B cell or T cell lineages, considering the shared developmental origins of these lymphocytes?

Considering the phenomenon of receptor editing in B cells, what cellular mechanisms guide B cells to re-engage the V(D)J recombination machinery specifically at the light chain locus, particularly following recognition of self-antigen by a newly formed IgM receptor?

During the development of T cells, lineage commitment to αβ T cells and γδ T cells are thought to be mutually exclusive. How would disruption of intercellular signaling during T cell development specifically influence cell fate?

Considering the structural basis for V(D)J recombination, what mechanisms prevent the joining of two V gene segments directly to each other without an intervening D gene segment in heavy chain loci?

What cellular mechanisms orchestrate the egress of mature, naïve T cells from the thymus into the peripheral circulation, ensuring their proper distribution and function within secondary lymphoid organs?

During negative selection, what signal would result in T cell apoptosis and how does this affect the overall populations of future T cells?

Immature thymocytes in the outer cortex of the thymus are subjected to a barrage of signaling and tolerance protocols, how does lack of IL-7 or improper pre-TCR signalling effect progression through the thymus?

The AIRE protein is important for expression of tissue restricted antigens (TRA). TRA presentation is regulated by two distinct populations of thymic cells. If these cells aren't able to present TRA-MHC complexes, what are the overall immunological consequences?

Severe Combined Immunodeficiency (SCID) is a group of rare disorders caused by mutations in different genes involved in the development and function of immune cells. Mutations in RAG1/2 cause SCID, which is distinct from other types of T- and B- SCID. The RAG proteins perform what essential step in lymphocyte production?

Considering the degeneracy inherent in codon-amino acid relationships, what specific mechanism during junctional diversity is most likely to mitigate the potential for frameshift mutations while maximizing amino acid variability at the V(D)J junctions?

Given that RAG1/2 proteins are responsible for the initial DNA cleavage during V(D)J recombination, how does the cell ensure that cleavage occurs precisely at the border between the coding sequence and the flanking recombination signal sequences (RSSs), thus preventing damage to the coding sequence?

In the development of γδ T cells, what unique characteristic of their TCR repertoire and antigen recognition allows them to respond rapidly to stress signals and infections without prior sensitization, contrasting with the antigen-dependent activation of αβ T cells?

Given that IL-7 is crucial for early lymphocyte progenitor survival and proliferation, and that mutations in the IL-7 receptor (IL-7R) can lead to SCID, what is the most likely molecular mechanism by which loss of IL-7 signaling impairs V(D)J recombination?

During negative selection, what feature of T-cell to mTEC binding will result in apoptotic-linked clonal deletion?

Considering the phenomenon of somatic hypermutation (SHM) within germinal centers, what mechanism prevents AID-mediated cytosine deamination from indiscriminately mutating the entire genome, leading to genomic instability and cellular transformation?

Considering the activity of somatic hypermutation (SHM) in B cells, what cellular mechanisms limit AID-induced damage?

Mutations in the RAG1/2 genes can lead to Omenn syndrome, which is characterized by oligoclonal T cells. What is the most plausible mechanism by which mutations in RAG1/2 could lead to Omenn syndrome?