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Questions and Answers
Which of the following ways do CSR and V(D)J recombination differ? (Select all that apply)
Which of the following ways do CSR and V(D)J recombination differ? (Select all that apply)
What are the substrates for CSR?
What are the substrates for CSR?
Constant region genes in heavy chain.
How does AID work?
How does AID work?
Converts C to U by deamination reaction.
What regulates specific class switch events?
What regulates specific class switch events?
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Why are antibodies widely used?
Why are antibodies widely used?
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What is Ig Class Switch Recombination (CSR)?
What is Ig Class Switch Recombination (CSR)?
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What is required for a B cell to switch isotopes?
What is required for a B cell to switch isotopes?
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Where do isotype switching and affinity maturation occur?
Where do isotype switching and affinity maturation occur?
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What regions determine antibody isotype?
What regions determine antibody isotype?
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What does class switching affect regarding antibodies?
What does class switching affect regarding antibodies?
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What are the roles of AID and UNG in class switching?
What are the roles of AID and UNG in class switching?
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Are T cells important in class switching?
Are T cells important in class switching?
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How is diversity established in BCR and TCR?
How is diversity established in BCR and TCR?
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What happens if there is a mutation in AID or UNG?
What happens if there is a mutation in AID or UNG?
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Why is class switching important?
Why is class switching important?
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What defines affinity maturation?
What defines affinity maturation?
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What occurs during somatic hypermutation?
What occurs during somatic hypermutation?
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What mechanisms regulate somatic hypermutation?
What mechanisms regulate somatic hypermutation?
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What happens to B cells after SMH and affinity maturation?
What happens to B cells after SMH and affinity maturation?
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What are the important steps in memory B cell development?
What are the important steps in memory B cell development?
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How do different heavy chain constant regions affect antibodies?
How do different heavy chain constant regions affect antibodies?
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What generates diversity in the Ig repertoire?
What generates diversity in the Ig repertoire?
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What is combinational diversity?
What is combinational diversity?
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What is junctional diversity?
What is junctional diversity?
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What are the effector functions of antibodies?
What are the effector functions of antibodies?
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What are the major enzymes involved in class switch recombination?
What are the major enzymes involved in class switch recombination?
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RAG 1/2 are required for isotype switching.
RAG 1/2 are required for isotype switching.
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When and where does class switching recombination occur?
When and where does class switching recombination occur?
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What distinguishes VDJ recombination from CSR?
What distinguishes VDJ recombination from CSR?
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What is the difference between CSR and SHM?
What is the difference between CSR and SHM?
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How do BCR and TCR differ?
How do BCR and TCR differ?
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Study Notes
Class Switch Recombination (CSR) vs V(D)J Recombination
- CSR and V(D)J recombination involve different processes and signal pathways.
- V(D)J recombination occurs randomly in the bone marrow and involves both heavy and light chains, while CSR is regulated and occurs in germinal centers, affecting only heavy chains.
- V(D)J produces antibodies with different specificities, while CSR changes effector functions without altering specificity.
- V(D)J recombination requires RAG-1 and RAG-2 proteins, while CSR relies on AID and UNG enzymes.
Substrates and Key Factors
- CSR targets constant region genes in the heavy chain, performed in the germinal center with AID, UNG, and APE involved.
- Somatic Hypermutation (SHM) affects the variable regions of both heavy and light chains, also occurring in the germinal center.
Mechanism of AID
- AID converts cytosine (C) to uracil (U) through deamination, operating at variable and switch regions during CSR.
Regulation of Class Switch Events
- Class switch events are regulated by cytokines and the CD40L:CD40 interaction.
- IL-4 induces IgG1 and IgE, IL-5 prompts IgA augmentation, IFN-y induces IgG3 and IgG2a, TGF-β leads to IgG2b, and IL-21 promotes IgG1, IgG3, and IgA.
Antibody Functions in Research and Therapy
- Antibodies are versatile lab reagents, diagnostic tools, and therapeutics due to their ability to act distally, recognize antigens with high specificity, and have variable effector functions.
Overview of Class Switch Recombination
- CSR replaces IgM/IgD with other isotypes, maintaining the antigen-binding site but altering effector properties.
- Only B cells undergo CSR, which is specific to regions.
Determinants of B Cell Isotope Switching
- Upon leaving the bone marrow, B cells express IgM and IgD and can switch to IgG, IgA, or IgE during immune responses.
- Whereas V(D)J recombination is random, CSR is an instructive process initiated by cytokine signals.
Isotype Switching and Affinity Maturation Location
- Both processes occur in germinal centers after stimulation of mature B cells.
Antibody Isotype Determination
- The heavy chain constant regions dictate antibody isotype.
- Immature B cells express IgM and IgD, while mature B cells express IgG, IgA, or IgE.
Effects of Class Switching on Antibody Function
- Class switching affects the effector function of antibodies without altering the binding affinity for specific antigens, as the V(D)J sequence remains unchanged.
Enzymatic Roles in Class Switching
- AID alters single-stranded DNA, converting C to U; UNG removes U, and APE generates nicks, facilitating double-strand breaks at switch regions.
T Cells' Role in Class Switching
- Activation of B cells by protein antigens and helper T cells induces AID expression and migration into germinal centers.
Comparison of TCR and BCR
- TCR acts only as an antigen-specific receptor, while BCR functions as both a receptor and an effector molecule, with diversity achieved through isotype switching and affinity maturation.
Implications of AID or UNG Mutations
- Mutations in AID or UNG disrupt class switch recombination and somatic hypermutation, impacting B cell receptor diversity.
Importance of Class Switching
- Class switching is crucial as it alters antibody effector functions, without improving affinity toward the antigen.
Affinity Maturation Process
- Occurs through clonal selection of high-affinity B cells in germinal centers, with competition for antigens presented by follicular dendritic cells.
Somatic Hypermutation (SHM)
- SHM diversifies variable regions through point mutations, enhancing antigen binding, and is restricted to B cells in germinal centers.
Outcomes of Somatic Hypermutation
- Possible outcomes include increased affinity, decreased affinity, unchanged affinity, loss of specificity, or a change in specificity due to mutations.
Dangers of SHM
- Potential for "horror autotoxicus," where SHM may lead to self-reactive B cells, but checkpoints exist to prevent this.
Fate of B Cells Post-SMH
- B cells that pass through SMH and affinity maturation differentiate into plasma cells or memory B cells, with plasma cells secreting high-affinity antibodies.
Key Steps in Memory B Cell Development
- Involvement of isotype switching, clonal expansion, somatic hypermutation, and affinity maturation to ensure long-lasting immune responses.
Diversity of Immunoglobulin Repertoire
- Generated through combinational diversity, junctional diversity, somatic hypermutation, and isotype switching.
Functions of Antibodies
- Neutralization of pathogens, opsonization for phagocytosis, and complement activation enhance immune responses.
Major Enzymes in Class Switch Recombination
- AID facilitates cytidine deamination, UNG creates basic sites, and APEI generates nicks necessary for recombination.
Class Switching Requirements
- RAG-1 and RAG-2 are not required for isotype switching; this process relies on different enzymatic mechanisms.
Timing and Location of CSR vs. SHM
- CSR occurs in germinal centers post-B cell stimulation, while SHM occurs during antibody responses, also within germinal centers.
Distinctions Between VDJ and CSR
- VDJ is random, affects both T and B cells in the bone marrow, while CSR is instructed, only impacting heavy chains in B cells.
Differences Between CSR and SHM
- CSR modifies heavy chain constant regions, involving different enzymes, while SHM further diversifies variable regions through point mutations.
BCR vs TCR Characteristics
- BCR can recognize both free and MHC-bound antigens, undergoes CSR and SHM, while TCR only recognizes MHC-bound antigens and does not undergo CSR or SHM.
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Test your knowledge on the differences between Class Switch Recombination (CSR) and V(D)J recombination in immunology. This quiz will help you understand key concepts and mechanisms involved in antibody function and B-cell development. Perfect for students eager to master the intricacies of immunological processes.
