Lecture 31 - B cells Flashcards
What are the main components of the TCR structure?
The TCR is composed of an α chain and a β chain, each with a variable and constant region.
What gene segments are present in the α and β chain loci of the TCR?
- α chain locus: Multiple V and J segments
- β chain locus: Multiple V, D, and J segments
Where does TCR somatic recombination occur, and is it reversible?
TCR somatic recombination occurs in the thymus and is irreversible.
What is the order of recombination in the α and β chains of TCR?
α chain: VJ recombination
β chain: D-J recombination occurs first, followed by V-DJ recombination
What is the significance of α and β chain combination in TCR formation?
The combination of α and β chains creates the unique antigen-binding specificity of the TCR.
How is V(D)J recombination in TCR similar to BCR recombination?
- V, D, and J segments are flanked by Recombination Signal Sequences (RSS)
- RAG-1/2 recognize these sequences
- Artemis cuts the DNA hairpins
- TdT adds non-coded nucleotides in the joining regions
How does the arrangement of RSS differ between Ig heavy chains and TCR β chains?
- Ig heavy chain: D segment is surrounded by two RSS, both with 12-bp spacing
- TCR β chain: D segments have a 5’ 12-bp RSS and a 3’ 23-bp RSS
How many Complementarity-Determining Regions (CDRs) does each TCR chain have?
Each TCR chain has 3 CDRs.
What is the significance of CDRs in TCR structure?
CDRs are the sites with the most diversity in the TCR, allowing for antigen recognition.
Which CDR is particularly important for TCR diversity?
CDR3 is the most important source of diversity
Where are CDR1 and CDR2 encoded in the TCR?
CDR1 and CDR2 are encoded within the V segments of the α and β chains.
Where is CDR3 encoded in the TCR?
In the β chain, CDR3 is encoded in the D and J segments.
In the α chain, CDR3 is encoded between the V and J segments.
What is the purpose of allelic exclusion in B cells?
Allelic exclusion ensures that each B cell synthesizes only one allele for a heavy chain and one allele for a light chain to maintain antigen specificity.
What happens once a B cell receptor (BCR) is expressed on the cell surface?
The BCR sends a signal to silence the other allele, preventing it from being expressed.
How is the other chromosome silenced in allelic exclusion?
The other chromosome becomes methylated, making it inaccessible to transcription machinery.
Why is genomic silencing of the other chromosome important in B cells?
It ensures that each B cell expresses only one version of the BCR, maintaining consistent antigen specificity.
Which two immunoglobulins are part of the first wave of secreted antibodies?
IgM and IgD
What immunoglobulins do mature naïve B cells express on their surface?
Transmembrane IgM and IgD
What is the sequence of IgM and IgD expression in B cells?
- Newly formed B cells initially express IgM as their primary BCR.
- Later, some B cells switch to expressing IgD.
- This results in co-expression of IgM and IgD on the B cell surface.
What happens when a mature naïve B cell receives activation signals (Signal 1 & 2)?
Some B cells form a primary focus and differentiate into plasmablasts, which can secrete antibodies.
How do B cells switch from membrane-bound to secreted antibody forms?
Through alternative RNA splicing, which allows the same primary mRNA transcript to be differentially spliced into either:
- Secreted antibody mRNA
- Transmembrane antibody mRNA
How does alternative RNA splicing influence Ig subtype production?
It enables B cells to switch Ig expression without DNA recombination, allowing for secretion of different antibody isotypes.
What are the five isotypes of heavy chains in immunoglobulins (Igs)?
μ (IgM), δ (IgD), γ (IgG), α (IgA), ε (IgE)
What are the five main classes of immunoglobulins (Igs)?
IgM
IgD
IgG
IgA
IgE
Which Ig classes have variants?
IgG and IgA have different subclasses.
Where does the switch from producing standard IgM and IgD to other Ig classes occur?
In the secondary lymphoid follicle, also known as the germinal center.
What processes do B cells undergo in the germinal center to produce more effective antibodies?
- Somatic hypermutation
- Affinity maturation
- Class switching
Where does secondary diversification of B cells occur?
In the germinal center of secondary lymphoid organs after the B cell receives signals 1 & 2 again.
What are the two key processes involved in secondary diversification?
- Somatic hypermutation – Increases affinity for the antigen while keeping specificity the same.
- Class switching – Replaces one heavy chain constant region with a different isotype.
Do these mechanisms act on already rearranged Ig genes?
Yes! V(D)J recombination has already occurred in the variable region, so you can’t go back.
Where does somatic hypermutation occur, and what does it do?
- Occurs in activated B cells in peripheral lymphoid organs, particularly in germinal centers.
- Causes a high rate of point mutations in the V gene sequences to improve antigen binding.
What is affinity maturation?
The selection of mutated B cells with higher affinity for the antigen, ensuring that only the best B cells survive and proliferate.
When does affinity maturation occur?
It happens during secondary or tertiary immune responses, leading to the production of higher-affinity antibodies over time.
What signals B cells to undergo class switching?
Cytokines secreted by T follicular helper (TFH) cells in the germinal center.
Give an example of a cytokine that induces class switching.
IL-4 (a Type 2 response cytokine) induces IgE production.
When does class switching occur?
Only after B cell activation (after receiving signals 1 & 2).
Is class switching reversible?
No, class switching is irreversible.
What guides class switch recombination?
Switch (S) regions located upstream of each constant (C) gene.
