Heavy and Light Chains

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Questions and Answers

Which of the following represents the correct order of events during B cell maturation in the bone marrow concerning immunoglobulin gene rearrangement?

  • Constant region rearrangement, followed by variable region rearrangement in both heavy and light chains.
  • Simultaneous rearrangement of heavy and light chain variable regions.
  • Light chain variable region rearrangement, followed by heavy chain variable region rearrangement.
  • Heavy chain variable region rearrangement, followed by light chain variable region rearrangement. (correct)

In the rearrangement of the light chain variable region, which gene segments directly encode the variable region of the light chain after being rearranged?

  • B and J gene segments. (correct)
  • D and J gene segments.
  • V and J gene segments.
  • V and C gene segments.

If a developing B cell fails to successfully rearrange its heavy chain variable region genes, what is the most likely outcome?

  • The cell proceeds directly to light chain rearrangement, skipping heavy chain rearrangement.
  • The cell switches to expressing only the light chain, pairing it with a surrogate heavy chain.
  • The cell undergoes apoptosis due to its inability to produce a functional B cell receptor. (correct)
  • The cell attempts to rearrange the heavy chain genes multiple times until successful.

What is the primary role of the error-prone enzyme TdT (terminal deoxynucleotidyl transferase) during VDJ rearrangement?

<p>To introduce random N nucleotides at the joining sites of gene segments, increasing antibody diversity. (D)</p> Signup and view all the answers

Which of the following best describes the function of recombination signal sequences (RSS) in VDJ rearrangement?

<p>They act as recognition sites for enzymes that mediate DNA cutting and joining. (D)</p> Signup and view all the answers

How does the heavy chain variable region rearrangement differ fundamentally from light chain rearrangement in terms of the initial steps?

<p>The heavy chain involves rearrangement of V, D, and J segments, while the light chain only involves V and J segments. (B)</p> Signup and view all the answers

Once heavy chain gene rearrangement is successfully accomplished, what is the immediate outcome in terms of gene expression?

<p>Transcription of the entire heavy chain gene, leading to the production of μ or δ chains. (B)</p> Signup and view all the answers

Mature B cells expressing both IgM and IgD on their cell surface with identical antigenic specificity are the result of what process?

<p>Alternative splicing of the heavy chain transcript, allowing for different constant regions to be attached. (D)</p> Signup and view all the answers

What would be the most likely consequence if the RAG1 and RAG2 enzymes were non-functional in a developing B cell?

<p>Failure to initiate VDJ rearrangement, resulting in a lack of antibody diversity. (A)</p> Signup and view all the answers

After a heavy chain gene has undergone VDJ rearrangement and is successfully expressed, the B cell rapidly proliferates. What is the significance of pairing this rearranged heavy chain with a variety of light chains?

<p>It allows greater diversity in antigen recognition, as each heavy-light chain combination may have a unique specificity. (B)</p> Signup and view all the answers

Flashcards

Antibody Diversity

The diversity of antibody specificity in response to foreign antigens, based on the organization of the immunoglobulin gene variable Region.

Gene Rearrangement Order

The ordered sequence during B cell maturation in the bone marrow where heavy chain variable Region rearranges first, followed by the light chain variable Region.

Light Chain Families

Kappa and lambda light chain families contain V, J, and C gene segments. The rearranged VJ segments encode the variable Region of the light chain.

Class Switching

Process where rearrangement of the heavy chain variable Region is proceeded by rearrangement of constant regions.

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Heavy Chain Joining

Heavy chain first joins a D gene segment to a J segment, then the resulting DJ segment joins a V segment to generate a VDJ segment.

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IgM and IgD Expression

Mature B cells expressing both IgM and IgD with identical antigenic specificity on the cell surface after heavy chain gene rearrangement.

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VDJ Rearrangement Goal

To create a massive amount of unique antigen receptors on T and B cells.

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Recombination Signal Sequence

Made up of a heptamer Non number and either a 12 or 23 base pair spacer.

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TDT Enzyme

Adds N nucleotides at joining sites, and then the DNA is ligated together.

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Study Notes

  • The immune system can produce a diverse range of antibody specificities in response to a seemingly endless array of foreign antigens.
  • This diversity lies in the organization of the immunoglobulin gene variable region.
  • Gene rearrangement happens in a specific order as B cells mature in the bone marrow, with the heavy chain variable region rearranging before the light chain.

Light Chain Variable Region

  • Kappa and lambda light chain families have distinct characteristics, including V, J, and C gene segments.
  • The rearranged VJ segments code for the light chain's variable region.
  • Light chain VJ rearrangement steps:
  • Recognition of recombination signal sequences.
  • Cleavage of one DNA strand by RAG1 and RAG2.
  • Creation of a hairpin structure at the cut.
  • Cutting the hairpin and adding P-region nucleotides.
  • Adding up to 15 N-region nucleotides to the cut ends of V and J coding sequences.
  • Repair and ligation to connect signal sequences.

Heavy Chain Variable Region

  • Variable region gene rearrangement creates mature B cells that produce diverse antibodies.
  • Heavy chain variable region rearrangement precedes constant region rearrangement through class switching.
  • The heavy chain's size requires two separate rearrangement events within the variable region.
  • Unlike the light chain, the heavy chain first combines a D gene segment with a J segment.
  • The resulting DJ segment then joins a V segment to form a VDJ segment, which encodes the entire variable region.
  • Heavy chain gene rearrangement steps are the same as light chain rearrangement, but with extra steps to join DJ segments to V segments to form the final VDJ heavy chain genes.
  • After heavy chain gene rearrangement, RNA polymerase binds to the promoter sequence and transcribes the entire heavy chain gene.
  • Production of the mu or delta chain results in mature B cells that express both IgM and IgD with identical antigenic specificity on the cell surface.

VDJ Rearrangement Summary

  • VDJ rearrangement creates a large number of unique antigen receptors on T and B cells.
  • During VDJ rearrangement, the cell randomly selects from inherited V, D, and J regions.
  • Cuts are made in the DNA sequence at precise locations signaled by recombination signal sequences.
  • Recombination signal consists of a heptamer, nonamer, and either a 12 or 23 base pair spacer.
  • The error-prone enzyme TDT fills in the cuts, adding N nucleotides at joining sites, and then the DNA is ligated together.
  • After a cell completes rearrangement of a beta chain or heavy chain, it rapidly proliferates and that chain is paired with a variety of alpha or light chains.

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