Immune System B Cell Development Quiz
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Questions and Answers

What chemokines attract immature B cells to the lymph node?

  • CCL21 and CXCL9
  • CCL22 and CCL17
  • CXCL12 and CCL19
  • CCL19 and CCL21 (correct)

How do immature B cells enter the lymph node?

  • By direct transfer from lymphatic vessels
  • Through passive diffusion
  • Via blood capillaries only
  • Through high endothelial venules (HEV) (correct)

Which specialized cells interact with immature B cells in the lymph node?

  • Peripheral blood mononuclear cells
  • Cortical thymic epithelial cells
  • Follicular dendritic cells (FDC) (correct)
  • Lymphatic endothelial cells

What role do the chemokines CCL19 and CCL21 play in lymph node architecture?

<p>They aid in the attraction of B cells to lymph nodes (D)</p> Signup and view all the answers

What is the primary function of follicular dendritic cells (FDC) in the lymph node?

<p>To interact with and stimulate immature B cells (A)</p> Signup and view all the answers

What process is responsible for eliminating self-reactive B cells?

<p>Negative selection (D)</p> Signup and view all the answers

What can happen if B cells are over-expressed?

<p>They may contribute to cancer (B)</p> Signup and view all the answers

What is the end result after B cells proliferate and differentiate upon activation?

<p>They produce antibodies (B)</p> Signup and view all the answers

During B cell development, which selection process ensures the generation of B cells with unique B cell receptors (BCRs)?

<p>Positive selection (D)</p> Signup and view all the answers

Which of the following describes the correct trajectory of B cells from activation to function?

<p>Activated B cells become plasma cells and memory B cells (D)</p> Signup and view all the answers

Which gene is associated with Burkitt’s Lymphoma due to its role in cell cycle control?

<p>MYC (D)</p> Signup and view all the answers

What is the primary consequence of a defective BTK in B cell development?

<p>Impaired B cell signaling and maturation (D)</p> Signup and view all the answers

What event can convert a proto-oncogene into an oncogene?

<p>Chromosomal translocation and misexpression (A)</p> Signup and view all the answers

Which of the following types of genes can become oncogenes due to mutation or misregulation?

<p>Proto-oncogenes (B)</p> Signup and view all the answers

How do B cell tumors often arise according to the content provided?

<p>Through chromosomal translocations and oncogene activation (A)</p> Signup and view all the answers

What role does the BCL2 proto-oncogene play in B cell lineage?

<p>Protects from premature apoptosis (C)</p> Signup and view all the answers

Why is the continual production of MYC protein problematic in B cells?

<p>It causes uncontrolled growth and division (B)</p> Signup and view all the answers

What might occur if B cells acquire additional mutations after MYC translocation?

<p>Development of cancer (D)</p> Signup and view all the answers

What factor do immature B cells need to survive and mature in the primary follicle?

<p>CXCL13 (C)</p> Signup and view all the answers

How do most immature B cells die in the primary follicle?

<p>By apoptosis (C)</p> Signup and view all the answers

What is the consequence for mature B cells if they do not encounter a specific antigen?

<p>They die within ~100 days (A)</p> Signup and view all the answers

What is a characteristic of B cell deficiency diseases?

<p>Impaired antibody production (A)</p> Signup and view all the answers

Which condition is associated with a lack of antibodies being produced?

<p>X-linked agammaglobulinemia (A)</p> Signup and view all the answers

What process increases the chance of malignant transformation in B cells?

<p>Lack of interaction between B cells and T cells (A)</p> Signup and view all the answers

What is a common outcome for anergic B cells that enter lymph nodes?

<p>They undergo apoptosis (C)</p> Signup and view all the answers

What is the role of B cell activating factor (BAFF)?

<p>Promotes B cell proliferation and survival (C)</p> Signup and view all the answers

What triggers apoptosis in B cells that fail to competitively enter primary follicles?

<p>Intrinsic molecular defects (A)</p> Signup and view all the answers

Which of the following is NOT considered a B cell tumor?

<p>X-linked agammaglobulinemia (B)</p> Signup and view all the answers

What is the role of dendritic cells in the 2° lymphoid tissue?

<p>Present antigenic peptides with MHC-I and MHC-II (C)</p> Signup and view all the answers

Which signal is NOT required for B cell activation?

<p>Secretion of cytokines by Naïve CD8 T cells (A)</p> Signup and view all the answers

What do activated B cells differentiate into?

<p>Plasma cells and memory B cells (C)</p> Signup and view all the answers

Which of the following is primarily secreted by plasma cells?

<p>High-affinity IgG antibodies (A)</p> Signup and view all the answers

What type of molecules do B cell coreceptors bind to during activation?

<p>C3d on antigens (B)</p> Signup and view all the answers

What is a characteristic of Naïve CD4 T cells when they enter 2° lymphoid tissue?

<p>They are activated by dendritic cells with MHC-II (A)</p> Signup and view all the answers

What is the initial type of antibody secreted by newly activated plasma cells?

<p>IgM (C)</p> Signup and view all the answers

Which statement about B cells is true?

<p>B cells can circulate through all secondary lymphoid tissues. (D)</p> Signup and view all the answers

What is the primary location where B-cell development begins?

<p>Bone marrow (C)</p> Signup and view all the answers

Which of the following stages is characterized by the rearrangement of heavy chain gene segments?

<p>Pro-B cell (B)</p> Signup and view all the answers

What occurs during junctional diversity in B-cell development?

<p>It allows for up to 1.8 million unique combinations (D)</p> Signup and view all the answers

Which component is NOT a part of the pre-B-cell receptor assembly?

<p>IgM antibody (D)</p> Signup and view all the answers

Why do B cells undergo receptor editing?

<p>To ensure self-reactive BCRs are eliminated (B)</p> Signup and view all the answers

What defines positive selection in B cell development?

<p>Failure to bind to self-antigens (D)</p> Signup and view all the answers

Which light chain gene segments are rearranged first during B-cell development?

<p>Kappa light chain segments (B)</p> Signup and view all the answers

What happens to B cells that fail positive selection?

<p>They enter apoptosis (C)</p> Signup and view all the answers

Which of the following describes clonal deletion in B cell development?

<p>Eliminates self-reactive B cells (A)</p> Signup and view all the answers

What is the role of Bone Marrow Stromal Cells in B cell development?

<p>Provide a supportive environment (B)</p> Signup and view all the answers

Which is true about self-tolerant immature B cells?

<p>Leave the bone marrow for maturation (C)</p> Signup and view all the answers

What does allelic exclusion in B cell development ensure?

<p>Each B cell produces monospecific antibodies (C)</p> Signup and view all the answers

During which stage do heavy chain rearrangements predominantly take place?

<p>Pre-B cell (B)</p> Signup and view all the answers

Anergic immature B cells primarily make which of the following?

<p>IgD (A)</p> Signup and view all the answers

Flashcards

Dendritic Cells (DCs)

Specialized immune cells that present processed antigens (peptides) to T cells using MHC-II molecules, initiating an immune response.

Helper T cells (TH or CD4+ T cells)

A type of T cell that helps activate B cells and other immune cells. They express CD4 and interact with MHC-II presented antigens.

Cytotoxic T cells (CTL or CD8+ T cells)

A type of T cell that directly kills infected cells. They express CD8 and interact with MHC-I presented antigens.

Naïve B cell

A type of B cell that has not yet encountered its specific antigen. They reside in secondary lymphoid tissues.

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B cell receptor (BCR)

The antigen receptor expressed on the surface of B cells. It binds to specific antigens, initiating B cell activation.

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B cell activation

A process by which B cells differentiate into plasma cells and memory B cells. This involves proliferation and antibody production.

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Plasma cell

A specialized type of B cell that produces large quantities of antibodies. These antibodies are directed against the specific antigen that activated the B cell.

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Memory B cell

A long-lived B cell that retains the memory of a previous encounter with an antigen. These cells are ready to quickly respond to future exposures to the same antigen.

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Follicular Dendritic Cells (FDC)

Specialized stromal cells located in lymph nodes that play a crucial role in B cell development and antibody responses.

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High Endothelial Venules (HEV)

Small blood vessels in lymph nodes that allow immature B cells to exit the bloodstream and enter the lymph node.

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Chemokines

Chemical messengers that attract immature B cells to the lymph node, playing a crucial role in their migration.

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CCL21

A type of chemokine produced by stromal cells in the lymph node, attracting immature B cells.

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CCL19

A type of chemokine produced by dendritic cells in the lymph node, attracting immature B cells.

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Negative selection

A key step in B cell development where cells that can bind self-antigens are eliminated. This prevents the immune system from attacking the body's own tissues.

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Burkitt's Lymphoma

A type of B cell tumor characterized by the translocation of the MYC gene from chromosome 8 to an immunoglobulin gene on chromosome 2, 14, or 22. This leads to uncontrolled production of MYC protein, resulting in uncontrollable growth and division of B cells, eventually leading to cancer.

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BCL2 Proto-Oncogene

A protein that protects B cells from premature apoptosis by inhibiting cell death pathways. It is a proto-oncogene, meaning that its overexpression or deregulation can contribute to cancer development.

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Defective BTK

A genetic defect in the BTK (Bruton's tyrosine kinase) gene which is essential for B cell development and maturation. This defect prevents B cells from developing and maturing properly, leading to immunodeficiency.

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Proto-oncogenes

Genes that have the potential to cause cancer when they are expressed at the wrong time or in the wrong amounts. They are often involved in cell growth, proliferation, and differentiation.

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B Cell Lymphoma

A type of cancer that affects B cells. It is often characterized by chromosomal translocations and activation of proto-oncogenes.

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Intravenous Immunoglobulin Treatment

A type of treatment used to boost the immune system in patients with immunodeficiency disorders like defective BTK. It provides antibodies that the body is unable to produce on its own.

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Proto-Oncogenes

Genes that contribute to the regulation of cell growth and division. When mutated or abnormally expressed they can lead to cancer.

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MYC Gene

A key gene involved in cell cycle control. It is essential for regulating the growth and division of both normal and cancerous cells.

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BAFF

A soluble factor secreted by B cells and other lymphoid tissue cells that promotes B cell survival and maturation. It's essential for maintaining the integrity of the follicular dendritic cell network.

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Apoptosis of Immature B Cells

Immature B cells that fail to encounter their specific antigen in the primary follicle will undergo programmed cell death.

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Apoptosis of Mature B Cells

Mature B cells that fail to encounter their specific antigen in the periphery after leaving the secondary lymphoid tissues will also undergo programmed cell death after approximately 100 days.

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Anergic B Cells

A state of unresponsiveness in which B cells become unresponsive to their specific antigen. They may still enter lymph nodes but ultimately die by apoptosis.

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B Cell Deficiencies

A group of disorders characterized by impaired antibody production due to defects in B cell development, function, or interaction with other immune cells.

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B Cell Tumors

Uncontrolled proliferation of B cells, often resulting in tumors and malignancies. These tumors can be associated with chromosomal translocations and activation of proto-oncogenes.

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X-linked Agammaglobulinemia

A severe X-linked immunodeficiency characterized by the absence of mature B cells and a complete lack of antibody production.

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Common Variable Immunodeficiency (CVID)

A rare and severe immunodeficiency characterized by extremely low levels of all immunoglobulin (Ig) classes, particularly IgG. It typically presents in infancy.

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What determines the uniqueness of antigen-binding sites in B cells?

Unique antigen-binding sites are created by random combinations of V(D)J segments and light/heavy chains.

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What is junctional diversity?

Junctional diversity, referring to the addition of non-templated nucleotides during V(D)J recombination, adds further variations to the antigen-binding site.

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How many unique antigen-binding sites are theoretically possible?

The combination of V(D)J recombination and junctional diversity leads to an estimated 10^16 possible unique antigen-binding sites.

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What role do bone marrow stromal cells play in B cell development?

Bone marrow stromal cells provide a specialized microenvironment for B cell development.

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How do stromal cells interact with developing B cells?

Stromal cells express adhesion molecules like VLA-4 and VCAM-1, facilitating interactions with developing B cells.

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How do stromal cells support B cell survival and proliferation?

Stromal cells produce growth factors like SCF and IL-7, essential for B cell survival and proliferation.

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Where and when does heavy chain gene rearrangement occur?

The process of rearranging heavy chain genes begins in the bone marrow with the early pro-B cell stage and continues through the late pro-B cell stage.

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What are the two steps of heavy chain gene rearrangement?

Heavy chain genes undergo two key rearrangements: D + J followed by V + DJ.

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What is the role of the pre-B-cell receptor?

The pre-B-cell receptor acts as a quality control checkpoint, confirming the proper assembly of the μ heavy chain with the surrogate light chains.

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What happens if the μ heavy chain passes the pre-B-cell receptor test?

If the μ heavy chain can successfully bind to the surrogate light chains, the pre-B cell receptor will assemble in the ER, leading to the production of a large pre-B cell clone.

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What happens after heavy chain rearrangement?

After heavy chain rearrangement is complete, light chain gene rearrangement takes place in each individual small pre-B cell, ensuring a unique light chain for each B cell.

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What happens if the light chain fails to bind to the heavy chain?

The light chain must be able to bind to the heavy chain to form a functional BCR. If not, further rearrangement attempts are made.

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What are allelic and isotypic exclusion?

Allelic and isotypic exclusion ensure each B cell produces monospecific antibodies with the same antigen-binding site and a single type of light chain (kappa OR lambda).

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What happens to self-reactive immature B cells that bind to multivalent self-antigens?

Immature B cells that bind to multivalent self-antigens in the bone marrow undergo receptor editing, a process that attempts to rearrange the light chain genes to create a self-tolerant BCR.

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What happens to self-reactive immature B cells that bind to monovalent self-antigens?

Immature B cells that bind to monovalent self-antigens in the bone marrow become anergic, a state of unresponsiveness to antigens. They leave the bone marrow but die within a few days.

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Study Notes

Adaptive Immunity: B-Cell Mediated Immunity I

  • Activation of the Adaptive Immune Response
    • Dendritic cells enter secondary lymphoid tissue, presenting antigenic peptides with MHC-I and MHC-II.
    • Naïve CD4 T cells enter secondary lymphoid tissue, activated by dendritic cells with MHC-II.
    • Naïve CD8 T cells enter secondary lymphoid tissue, activated by dendritic cells (or dendritic cells + TH1) with MHC-I.
    • Naïve B cells enter secondary lymphoid tissue, activated by T follicular helper (TFH) cells.

Naïve B Cells

  • Enter secondary lymphoid tissue from blood/lymph.
  • Use B cell receptors (BCRs) to scan unprocessed antigens on follicular dendritic cells (or macrophages).
  • Endocytose BCR:antigen complexes, process, and present peptides with MHC-II to TFH cells.
  • Activated B cells proliferate and differentiate into plasma cells and memory B cells.
  • TFH cells provide cytokines (IL-21, IL-6, etc.) to influence this process.
  • Activation requires 3 signals: BCR and co-receptor cooperation; BCRs cross-linked by intact antigens; B cell co-receptor molecules (CR2, CD19, CD81) bind C3d (on antigen). CD40 binds CD40L on TFH cells.

Plasma Cells = Effector B Cells

  • Initially secrete low-affinity IgM antibodies.
  • Some undergo affinity maturation and class switching (to secrete high-affinity IgG or other antibody classes).

BCR Gene Structure

  • Germline configuration of BCR/immunoglobulin genes inherited from egg and sperm.
  • Fragmented into several gene segments (L, V, D, J, C); multiple alleles.
  • Expression requires segment rearrangement and assembly into one complete functional gene.

BCR Gene Segments

  • Heavy-chain locus on chromosome 14: VH1, VH2, VH3, DH1-23, JH1-6, CH1-9.
  • Light-chain locus (к on chromosome 22; λ on chromosome 2): different Vs, Js, C segments.

Constant (C) Region Genes

  • Light chain: 4 or 5 Cᵝ gene segments possible.
  • к light chain: only 1 CR possible gene segment.
  • Heavy chain: 9 CH possible gene segments.

Somatic Recombination

  • Cutting and splicing of immunoglobulin gene segments during B cell development.
  • Light chain: one recombination event (~V+J).
  • Heavy chain: two recombination events (~D+J then V+DJ).
  • Creates diversity in antigen-binding sites in BCR and immunoglobulin.

Recombination Signal Sequences (RSSs)

  • Short DNA sequences flanking V, J, and D gene segments.
  • 12/23 rule: recombination occurs between two RSSs with different length spacers (12 & 23).

V(D)J Recombinase

  • Complex of enzymes carrying out somatic recombination in B cells.
  • RAG-1 and RAG-2 proteins are essential.
  • Cleaves RSSs at end of each heptamer; DNA ends recombined.
  • Coding joint creates functional V region exon.
  • Signal joint circularizes excised DNA.

Junctional Diversity

  • DNA sequence variations created in coding joints during V(D)J recombination.
  • Adds additional diversity to antigen-binding sites.
  • Includes P nucleotides (palindromic) and N nucleotides (non-templated) generated by terminal deoxynucleotidyl transferase (TdT).

B-Cell Tolerance: Receptor Editing and Anergy

  • Receptor editing mechanisms in immature B cells.
  • Recognize multivalent self-antigens, decreasing IgM and continuing to rearrange light chain genes.
  • New BCR is self-tolerant, the immature B cell matures.
  • New BCR is self-reactive then the process continues until a self-tolerant BCR is produced or cell runs out of light chain genes (apoptosis).
  • Anergy mechanisms in immature B cells recognizing monovalent self-antigens.
  • Make IgM and IgD but not active BCR.
  • Most die within one to five days.

B-Cell Maturation and Survival

  • Occurs in lymphoid follicles in secondary lymphoid tissues.
  • Immature B cells interact with follicular dendritic cells (FDCs) to complete maturation.
  • Mature B cells interact periodically with FDCs to survive.
  • Die in ~100 days if specific antigen not encountered.

B-Cell Abnormalities

  • B-cell deficiencies (X-linked agammaglobulinemia, X-linked immunodeficiency with hyper-IgM, etc.) can lead to problems with antibody production.
  • B-cell tumors feature uncontrolled growth and proliferation often linked to chromosomal translocations and proto-oncogenes activation.

Proto-oncogenes to Oncogenes

  • Proto- oncogenes (normal genes) regulate cell growth and division.
  • Mutations can transform them into oncogenes (cancer-causing genes), which are overexpressed, leading to uncontrolled proliferation.

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Test your knowledge on the role of chemokines and specialized cells in the development of B cells within the lymph node. This quiz covers the processes involved in B cell selection, activation, and their functions, including associated pathologies like Burkitt’s Lymphoma.

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