BLOCK 3: IMM: (3.3) ANTIBODIES (PT. 2)
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What process results in the diversity of immunoglobulins in B cells prior to encountering an antigen?

  • RNA splicing
  • Somatic hypermutation
  • Gene duplication
  • VDJ recombination (correct)

    • Which segments of DNA contribute to the assembly of a variable region of an immunoglobulin?

  • V, D, and J segments (correct)
  • V and C segments only
  • J and C segments only
  • C and J segments only

    • What is the main difference between secreted and membrane-bound antibodies?

  • They are encoded by different genes.
  • They differ in their C-terminal regions. (correct)
  • They are produced by different B-cell types.
  • They have different isotopes.

    • Which of the following accurately describes immunoglobulin isotypes?

    <p>They are differentiated by their constant regions.</p> Signup and view all the answers

    What is the role of the leader sequence in the immunoglobulin heavy-chain locus?

    <p>It directs the protein for cellular localization.</p> Signup and view all the answers

    How many functional Jκ gene segments are there in the κ light-chain locus?

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

    What is the significance of hybridomas in the context of monoclonal antibodies?

    <p>They only produce a single type of antibody.</p> Signup and view all the answers

    In the human immunoglobulin heavy-chain locus, how many functional VH gene segments are present?

    <p>40</p> Signup and view all the answers

    What is the primary purpose of V(D)J recombination in B cells?

    <p>To generate diverse antibody specificities</p> Signup and view all the answers

    What is the main role of alternative mRNA splicing in B cells?

    <p>To regulate the production of immunoglobulin isotypes</p> Signup and view all the answers

    Which component is part of the B cell receptor (BCR) complex?

    <p>Immunoglobulin heavy and light chains</p> Signup and view all the answers

    Which immunoglobulin isotypes are co-expressed in activated B cells?

    <p>IgM and IgD</p> Signup and view all the answers

    What distinguishes secreted antibodies from membrane-bound antibodies?

    <p>The use of different mRNA processing mechanisms</p> Signup and view all the answers

    What is the significance of junctional diversity in B cell development?

    <p>It contributes to the variation in immunoglobulin specificity</p> Signup and view all the answers

    During the creation of monoclonal antibodies, what is the initial step involving mouse lymphocytes?

    <p>They are stimulated by antigens to produce antibodies</p> Signup and view all the answers

    Which factor is crucial for the survival of hybridoma cells during monoclonal antibody production?

    <p>A drug that eliminates unfused lymphocytes</p> Signup and view all the answers

    What forms the functional B-cell receptor complex in B cells?

    <p>Immunoglobulin, Igα, and Igβ</p> Signup and view all the answers

    During alternative RNA processing in B cells, what determines the form of immunoglobulin produced?

    <p>The splicing of the transcript at specific sites</p> Signup and view all the answers

    What is the role of the carboxy terminus in the heavy-chain RNA of immunoglobulins?

    <p>It encodes the cytoplasmic domain of membrane-bound antibodies</p> Signup and view all the answers

    Which of these components is NOT associated with the B-cell receptor complex?

    <p>CD4</p> Signup and view all the answers

    What happens to the heavy-chain RNA when the transcript is processed for a secreted form of immunoglobulin?

    <p>Only the SC sequence is retained</p> Signup and view all the answers

    What type of immunoglobulin is primarily found as a B-cell receptor on the B-cell surface?

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

    Which process uniquely enhances immunoglobulin diversity in B cells?

    <p>VDJ recombination</p> Signup and view all the answers

    How do the heavy-chain C genes contribute to the differentiation of antibody forms?

    <p>Through alternative RNA splicing mechanisms</p> Signup and view all the answers

    What determines the choice between the secreted and membrane-bound forms of immunoglobulin during RNA processing?

    <p>The location of polyadenylation</p> Signup and view all the answers

    What is the significance of the long cytoplasmic tails of Igα and Igβ proteins?

    <p>They enable interaction with signaling proteins</p> Signup and view all the answers

    What is the correct order of immunoglobulin molecules as they appear during B cell development?

    <p>IgM, IgG, IgA, IgE</p> Signup and view all the answers

    Which immunoglobulin isotypes are co-expressed on the surface of a mature B cell?

    <p>IgM and IgD</p> Signup and view all the answers

    During isotype switching, which immunoglobulin molecule is typically produced first?

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

    What are the two types of IgA identified during B cell development?

    <p>IgA1 and IgA2</p> Signup and view all the answers

    What process allows a B cell to produce multiple types of immunoglobulins?

    <p>Alternative RNA splicing</p> Signup and view all the answers

    Which immunoglobulin is primarily expressed during the early stages of B cell development?

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

    Which immunoglobulin is associated with allergic responses?

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

    How many subclasses of IgG are there?

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

    Which immunoglobulin isotype is produced first during the splicing process?

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

    What immunoglobulin isotype results when an IgM heavy chain is swapped for an alpha heavy chain?

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

    In which scenario would both IgM and IgD be expressed on the surface of a B cell?

    <p>Due to their close proximity on the genome</p> Signup and view all the answers

    Which immunoglobulin isotype can switch from IgG to IgA?

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

    Which of the following best describes the relationship between IgM and IgD expression?

    <p>They are co-expressed due to gene proximity on the genome.</p> Signup and view all the answers

    What does isotype switching allow B cells to do?

    <p>Change antibody class without altering specificity</p> Signup and view all the answers

    Which immunoglobulin isotype would not typically be found on the same B cell as IgM?

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

    What is the result of V(D)J recombination in B cells?

    <p>Creation of diverse immunoglobulin variable regions</p> Signup and view all the answers

    What is the first step in the somatic recombination process for the heavy chain of immunoglobulins?

    <p>Merging of D and J segments</p> Signup and view all the answers

    In the formation of a functional light chain, what is combined with the variable region after VJ joining?

    <p>Constant region</p> Signup and view all the answers

    Which immunoglobulin molecule is produced when the constant mu region is selected during the heavy chain recombination process?

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

    During alternative mRNA splicing in B cells, what ultimately determines the specific form of immunoglobulin produced?

    <p>Choice of heavy chain constant regions</p> Signup and view all the answers

    What is the main function of the junctional diversity that occurs during B cell development?

    <p>To increase antigen diversity</p> Signup and view all the answers

    What key molecular event occurs at the membrane coding exons during immunoglobulin production?

    <p>Hydrophobic sequence addition</p> Signup and view all the answers

    Which of the following is a characteristic of the isotypes IgM and IgD co-expression in B cells?

    <p>This co-expression is essential for B cell activation</p> Signup and view all the answers

    Isotype switching in B cells largely depends on which of the following processes?

    <p>Selection of different heavy chain constant regions</p> Signup and view all the answers

    Study Notes

    Immunoglobulin Diversity in B Cells Before Antigen Encounter

    • Immunoglobulin is first made in a membrane-bound form that's present on the B-cell surface.
    • Igα and Igβ form a disulfide-linked complex that interacts with the immunoglobulin molecule.
    • Igα and Igβ have long cytoplasmic tails that interact with intracellular signaling proteins.
    • Igα and Igβ have binding sites for immunoglobulin C region on their extracellular portions.
    • The complex of immunoglobulin with Igα and Igβ serves as the functional B-cell receptor.
    • All isotypes can serve as B-cell receptors.
    • Igα and Igβ are also called CD79a and CD79b.

    Diversification of Antibodies After Antigen Encounter

    • Secreted antibodies are produced by an alternative pattern of heavy-chain RNA processing.
    • Each heavy-chain C gene has two exons (membrane-coding, MC & secretion-coding, SC) encoding the carboxy terminus.
    • Membrane-coding (MC) encodes the transmembrane region & cytoplasmic tail of the surface form.
    • Secretion-coding (SC) sequence encodes the carboxy terminus of the secreted form.
    • Alternative RNA processing determines whether a heavy-chain RNA will result in a secreted or transmembrane immunoglobulin.
    • Each heavy-chain C gene has two potential polyadenylation sites (pAμs & pAμm).
    • To generate the transmembrane form of the heavy chain, the transcript is cleaved and polyadenylated at the second polyadenylation site (pAμm).
    • Splicing between a site located between the fourth Cμ exon & SC sequence, & a second site at the 5ʹ end of MC exons, removes the SC sequence and joins MC exons to the fourth Cμ exon.

    The Structural Basis of Antibody Diversity

    • The DNA sequence encoding a V region is assembled from two or three gene segments.
    • The λ light-chain locus has ~30 functional Vλ gene segments, 4 pairs of functional Jλ, and a Cλ gene segment.
    • The κ light-chain locus has ~35 functional Vκ gene segments & 5 Jκ gene segments with ONE Cκ gene segment.
    • The heavy-chain locus has ~40 functional VH gene segments, a cluster of ~23 D segments, & 6 JH gene segments.
    • A monoclonal antibody is produced by a clone of antibody-producing cells.
    • To make a monoclonal antibody, lymphocytes from a mouse are immunized with an antigen of choice and fused with myeloma cells.
    • Fused cells are grown with a drug that kills myeloma cells but permits growth of hybrid cells.
    • Cultures of hybrid cells (hybridomas) are tested to determine whether they make the desired antibody.
    • Cultures containing a hybridoma making the desired antibody are cloned to produce a homogeneous culture of cells making the monoclonal antibody.
    • Myelomas are tumors of plasma cells; those used to make hybridomas were selected not to express antibody heavy and light chains.

    Overview

    • Epitope specificity of immunoglobulins is determined before antigen encounter.
    • The number of possible epitope-binding specificities is greater than the number of genes within the genome.
    • Each heavy-chain locus has multiple V, D, and J gene segments that are rearranged to produce a diverse array of antibodies.
    • This process is known as V(D)J recombination.
    • The rearrangement of these gene segments is mediated by specific enzymes, including RAG1 and RAG2.
    • Junctional diversity is generated during gene rearrangement, increasing the diversity of antibodies.
    • The process of V(D)J recombination contributes significantly to the diversity of the immune system.

    Immunoglobulin Heavy Chains

    • Immunoglobulin molecules are arranged in a specific order with IgM appearing first, followed by IgG, IgA and then IgE.
    • The order reflects the location of the heavy chain genes on the genome.
    • IgM and IgD genes are closely adjacent on the genome leading to their co-expression on the surface of B cells.
    • B cells express both IgM and IgD during development, but only express IgD upon maturation.
    • There are four subtypes of IgG (IgG1, IgG2, IgG3, and IgG4) and two subtypes of IgA (IgA1 and IgA2).
    • Each immunoglobulin domain is coded by a separate exon.

    Immunoglobulin Heavy Chain Assembly

    • During the assembly of heavy chains, the D and J segments recombine first, followed by the V segment.
    • The recombined VDJ region then joins with a constant region gene, determining the immunoglobulin class.
    • The constant region gene determines the class of the immunoglobulin molecule, such as IgM, IgG, IgA, or IgE.
    • Two membrane coding exons (MC) specify a hydrophobic sequence that anchors the immunoglobulin to the cell membrane.
    • This hydrophobic sequence will later be cleaved off during the maturation process.

    Immunoglobulin Light Chains

    • The light chains are assembled by recombining a variable segment (V) with a joining segment (J).
    • The VDJ region then joins with a constant region gene to produce a complete light chain.

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