BLOCK 3: IMM: (3.5) B-CELL DEVELOPMENT PART 1
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Questions and Answers

Where do the first three phases of B cell development occur?

  • Bone marrow (correct)
  • Thymus gland
  • Secondary lymphoid tissues
  • Spleen

    • What process occurs after the repertoire assembly in B cell development?

  • Positive selection
  • Nucleic acid rearrangement
  • Isotype switching
  • Negative selection (correct)

    • What differentiates B1 and B2 lineages in B cell development?

  • The types of antigens they recognize (correct)
  • The sites where they are produced
  • Their stages of positive selection
  • Their dependence on different cytokines

    • What is a common misconception about where positive selection occurs for B cells?

    <p>Only in bone marrow</p> Signup and view all the answers

    Which of the following techniques is NOT related to B cell development?

    <p>Transfusion compatibility testing</p> Signup and view all the answers

    How do B cells recirculate after development in the bone marrow?

    <p>They travel through blood and lymphoid tissues</p> Signup and view all the answers

    What is the primary function of somatic hypermutation in B cells?

    <p>To adjust B cell receptors for greater diversity</p> Signup and view all the answers

    Which phase follows the positive selection of B cells?

    <p>Clonal expansion</p> Signup and view all the answers

    What is a characteristic of isotype switching in B cells?

    <p>It deletes segments of DNA, making it irreversible.</p> Signup and view all the answers

    Which statement best describes somatic hypermutation?

    <p>It involves point mutations that are not reversed by the body.</p> Signup and view all the answers

    What happens to IgD after a B cell encounters an antigen?

    <p>It is lost from the surface as the cell matures.</p> Signup and view all the answers

    How does transcription regulation relate to B cell activation?

    <p>Surface IgM and IgD co-expression affects transcription activity.</p> Signup and view all the answers

    What role do point mutations play during somatic hypermutation?

    <p>They increase the mutation rate for higher affinity antibodies.</p> Signup and view all the answers

    Which aspect of transcriptional elements can be considered irreversible?

    <p>Changes due to point mutations in the genetic sequence.</p> Signup and view all the answers

    Which statement correctly reflects the relationship between isotype switching and DNA?

    <p>It permanently removes gene segments from the DNA.</p> Signup and view all the answers

    What technique did Winifred Ashby employ for her research on red blood cells?

    <p>Agglutination experiments to determine lifespan.</p> Signup and view all the answers

    What is the primary function of B1 cells in the immune system?

    <p>To generate antibodies directed against conserved sequences, typically carbohydrates</p> Signup and view all the answers

    Why are B1 cells important during fetal development?

    <p>They protect the fetus from maternal immune reactions against differing blood types.</p> Signup and view all the answers

    How does B1 cell immunity differ from B2 cell immunity?

    <p>B1 cells are fewer in number and respond to a more limited range of antigens.</p> Signup and view all the answers

    What role do natural antibodies primarily play in the immune response?

    <p>They are instinctually produced without previous exposure, targeting blood type antigens.</p> Signup and view all the answers

    Which of the following statements is true regarding the discovery of B1 cells?

    <p>They were discovered around 20 years ago.</p> Signup and view all the answers

    In the context of blood transfusions, how might B1 cells provide an advantage to a fetus?

    <p>By preventing maternal rejection of the fetus through natural antibodies against differing blood types.</p> Signup and view all the answers

    What is the likely impact of the limited isotype switching associated with B1 cells?

    <p>It restricts their ability to adapt to new pathogens.</p> Signup and view all the answers

    What is a characteristic feature of B1 cells in terms of their self-renewal capacity?

    <p>They can self-renew independently and without T-cell help.</p> Signup and view all the answers

    What role does interleukin-7 (IL-7) play in B cell development?

    <p>It promotes proliferation and survival of B cell progenitors.</p> Signup and view all the answers

    Which of the following signaling molecules is crucial for B cell receptor signaling?

    <p>Bruton’s Tyrosine Kinase (BTK)</p> Signup and view all the answers

    Which transcription factor is specifically associated with B cell activation?

    <p>Pax-5</p> Signup and view all the answers

    What is the function of integrin VLA-4 in B cell development?

    <p>It facilitates the binding of B cells to adhesion molecules on stromal cells.</p> Signup and view all the answers

    How do interactions between B cells and bone marrow stromal cells influence B cell development?

    <p>They promote the transition from pro-B to pre-B cell stages.</p> Signup and view all the answers

    What role does the FLT3 protein play in B cell development?

    <p>It helps differentiate stem cells into common lymphoid progenitors and B cell progenitors.</p> Signup and view all the answers

    What is the specific role of IL-7 in B cell maturation?

    <p>It is the receptor for IL-7 that is critical for signaling during early B cell development.</p> Signup and view all the answers

    Which of the following proteins is essential for the rearrangement of immunoglobulin genes in B cell development?

    <p>TdT</p> Signup and view all the answers

    Which polypeptides are known to make up the surrogate light chain in B cell development?

    <p>VpreB and λ5</p> Signup and view all the answers

    Which factor is directly associated with the signaling pathway that influences the differentiation of B cell precursors?

    <p>FLT3 ligand</p> Signup and view all the answers

    What is a primary function of Igα and Igβ in B cell development?

    <p>They signal for intracellular processes via their ITAMs.</p> Signup and view all the answers

    Which of the following proteins directly binds to the IL-7 receptor in the context of B cell maturation?

    <p>Kit</p> Signup and view all the answers

    Which stage of B cell development is characterized by the expression of a functional μ chain?

    <p>Large pre-B cell</p> Signup and view all the answers

    What role does FLT3 signaling play in B cell development?

    <p>Promotion of B cell survival and proliferation</p> Signup and view all the answers

    How does IL-7 influence B cell maturation?

    <p>It enhances lymphocyte proliferation and B cell differentiation</p> Signup and view all the answers

    Which of the following signaling molecules is essential for the transition of pro-B cells to pre-B cells?

    <p>BTK</p> Signup and view all the answers

    What transcription factor is critical for early B cell development and differentiation?

    <p>PAX5</p> Signup and view all the answers

    Which of the following best describes the interaction between B cells and bone marrow stromal cells?

    <p>Stromal cells provide survival signals and necessary adhesion molecules for B cell maturation</p> Signup and view all the answers

    Which CD marker is associated with pro-B cells and may influence differentiation events?

    <p>CD10</p> Signup and view all the answers

    What is a common characteristic of both B1 and B2 cells regarding activation pathways?

    <p>B2 cells are heavily dependent on helper T cell interactions, whereas B1 cells primarily respond to antigens directly</p> Signup and view all the answers

    What is the key function of transcription factors during the differentiation of B cells?

    <p>To activate genes necessary for B cell identity and function</p> Signup and view all the answers

    Study Notes

    B Cell Development

    • B cell development has six main phases:
      • Repertoire assembly (bone marrow)
      • Negative selection (bone marrow)
      • Positive selection (bone marrow)
      • Recirculation (lymphoid tissue)
      • Activation (lymphoid tissue)
      • Differentiation (lymphoid tissue)
    • Repertoire assembly forms the B cell receptor.
    • Negative selection occurs before positive selection.
    • Reversible modifications:
      • Transcriptional elements: irreversible process, involves co-expression of surface IgM and IgD
      • IgM and IgD expression: reversible due to loss of IgD after cell circulation
      • Splicing: reversible, involves changing the splicing and can be associated with isotype switching
    • Irreversible modifications:
      • Isotype switching: regulated process, occurs with subsequent encounters and cell division
      • Somatic hypermutation: point mutations in genomic DNA, not reversible, provides diversity at the antigen-binding site
    • Phases 1-3 occur in bone marrow
    • Phases 4-6 occur in secondary lymphoid tissue (lymph nodes, spleen)
    • B1 cells
      • Arise from the fetal liver during embryonic development
      • Provide early immune protection for the fetus
      • Possess limited isotype switching
      • Self-renew
      • Almost never requires T-cell help.
      • Mostly for conserved sequences, usually carbohydrates on bacteria
      • Predominantly found in areas of pathogen encounter (pleural and peritoneal cavities, upper respiratory and GI tract)
      • Produce many so-called "natural antibodies"
    • B2 cells
      • Make up the vast majority of B cells in the body.
    • Natural Antibodies
      • Directed against other blood types, potentially protecting the fetus from maternal immune rejection.
    • Winifred Ashby
      • First to establish that red blood cell lifespan in humans is longer than 2-3 weeks
      • Used agglutination to determine this.

    B Cell Development:

    • Occurs in 2 phases, 3 in the bone marrow and 3 in secondary lymphoid tissue
    • The first 3 phases of B cell development take place in the bone marrow.

    B Cell Development Markers:

    • CD127: α chain of the receptor for interleukin-7
    • CD19: a subunit of the B-cell co-receptor, cooperates with the antigen receptor to produce activating signals when antigen is bound.
    • CD34: Vascular addressin expressed on endothelial venules in lymph nodes and involved in the extravasation of white blood cells.
    • CD10: May have a role in inactivating regulatory peptides favoring differentiation events. Normally expressed on pro-B cells and mature germinal center B cells.

    B Cell Developmental Stages

    • Stem cells: Ig genes in the germline configuration
    • Early pro-B cell: Joining of DH to JH, defined by the rearrangement of the heavy chain, early pro-B cells turn into late pro-B cells
    • Late pro-B cell: Joining of VH to DJH
    • Large pre-B cell: Expression of a functional μ chain
    • Large pre-B cells proliferate, producing small pre-B cells: Rearrangement of the light chain gene occurs
    • Immature B cell: Successful light-chain gene rearrangement & expression of IgM on the cell surface

    Proteins Involved in B Cell Development

    • FLT3: Protein kinase and cell-surface receptor on stem cells, plays a crucial role in differentiation to CLP and B cell progenitor.
    • Kit: Acts as a receptor for stem cell factor (SCF)
    • IL-7R: Receptor for IL-7
    • RAG proteins: Essential for gene rearrangement, selectively expressed at the 2 stages where rearrangements are made.
    • TdT: Inserts N nucleotides in the VDJ recombination process.
    • VpreB & λ5: Polypeptides that form the surrogate light chain.
    • Igα & Igβ: Have long cytoplasmic tails with ITAMs that interact with intracellular signaling proteins & bind to the immunoglobulin C region on extracellular portions, forming the functional B-cell receptor complex.
    • CD19: Part of the BCR co-receptor and involved in intracellular signaling.
    • BTK: Kinase crucial for B cell receptor signaling.
    • Pax-5: Nuclear transcription factor & B cell-specific activator protein.

    B-cell Development: Role of Stromal Cells

    • Early stages of B-cell development are dependent on bone marrow stromal cells
    • Stem cells & early pro-B cells use integrin VLA-4 (Very Late Antigen 4) to bind to VCAM-1 (vascular cell adhesion molecule 1) on stromal cells
    • Interactions of other CAMs promote binding of Kit on the B cell to stem-cell factor (SCF) on the stromal cell
    • Activation of Kit causes B cell proliferation
    • Interleukin-7 (IL-7) plays a crucial role in the early development of B cells, promoting proliferation & survival of B cell progenitors during the transition from pro-B to pre-B cell stage.

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    Description

    Explore the intricacies of B cell development, which encompasses six main phases: repertoire assembly, negative selection, positive selection, recirculation, activation, and differentiation. Understand the reversible and irreversible modifications that influence B cell maturation, including transcriptional elements and isotype switching. This quiz will deepen your understanding of B cell biology in the immune system.

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