5 B-Lymphocytes Flashcards
*Q: Where does maturation of B lymphocytes take place? presence? What happens after? (2) What will each B cell be able to do?
A: B cell generation and maturation occurs in bone marrow in the absence of antigen
They migrate into the circulation and into lymphoid tissues
recognise a specific antigen
Q: What is the BCR? Consists of? (3) How does it function?
A: B Cell Receptor- where specificity resides -> unique binding site which binds to the epitope.
The BCR is a transmembrane protein complex consisting of a membrane-anchored antibody and di-sulphite linked heterodimers Igalpha and Igbeta- aids extracellular signal detection
When the BCR recognises an antigen, there is a structural change which drives signalling via Iga/Igb
Q: What leads to clonal selection of the B cell? What does it lead to? (2)
A: Each lymphocyte has a single, unique receptor
Interaction between BCR and antigen leads to activation
Activation causes proliferation of the relevant B cell
Q: Where does the main difference between B and T lymphocytes reside?
A: TYPE OF EPITOPE they recognise:
T cells - identify the sequence
B cells - identify the structure (tertiary)
Q: What are the two types of adaptive immune response?
A: Humoral: B cells - antibodies
Cell-Mediated: T cells - cytokines, killing
Q: What are Igalpha and Igbeta? Why are they useful? (2)
A: heterodimers- have an immunoglobulin like fold
The cytoplasmic tails of the mIg (membrane-bound Ig) is too short to signal
The cytoplasmic tails of Iga/Igb is long enough to interact with intracellular signalling molecules
Q: What generates antigen receptor diversity?
A: IMMUNOGLOBULIN GENE REARRANGEMENT/ recombination
*Q: What encodes the BCR? What happens during maturation? Essence?
A: Each BCR receptor chain is encoded by separate multigene families on different chromosomes
During B cell maturation these segments are rearranged and brought together
In essence, you produce a small number of building blocks which you can shuffle around and produce a lot of variety - happens in T and B cells
Q: How is a standard membrane protein expressed? (4)
A: Start off with genome DNA - exons and introns
Transcription - RNA produced
Splicing - RNA spliced
Translation - polypeptide produced
Q: How is the immunoglobin light chain expressed?
A: There are 70 variable units that people have - 40 in kappa and 30 in lambda- variable units exist in the genomic DNA in a cluster
B cells start in the bone marrow as immature B cells - they have germline DNA
As B cells develop, they get rid of most of the variable units and leave a few V and J regions (this is random)
So then the B cell has a variant version of this gene.
- > mRNA -> Different splicing patterns give rise to further variation
- > protein -> polypeptide
Q: Describe heavy chain gene rearrangement?
A: You start off with germline DNA
The different regions shuffle and rearrange via recombination
A few V, D and J regions are passed down
The constant region is what determines the type of antibody e.g. alpha constant region gene gives rise to IgA
- > mRNA -> Different splicing patterns give rise to further variation
- > protein -> polypeptide
Q: Does the heavy or light chain undergo gene rearrangement first?
A: Heavy Chain undergoes VDJ rearrangement FIRST
Light chain then undergoes VJ rearrangement
Q: How does a B cell start? Stimulated by? (2) What happens when B cells bind with antigens and transduces a signal through BCR? What else does this process require? 2 examples?
A: Starts as a naïve B cell
It is stimulated by antigens and interacts with T cells
Three Possible Pathways once it has recognised an antigen:
Affinity Maturation - antibody response improves
Memory Cell - becomes stored for later exposure to the same infection
Plasma Cell - B cells which physically make the antibody
Can’t be activated by antigen along: Naïve B cells require an accessory signal - this is costimulation
For B cells, accessory signals come from:
Directly from microbial constituents
T helper cell
Q: How is antibody production by B cells achieved? (2)
A: 2 pathways for 2 types of antigen that it can detect= T cell (thymus) dependent & T cell (thymus) independent
*Q: Explain the activation of B cells via T independent antigens. What type of antibody is produced?
A: Main thing it’s related to is polysaccharides
Because the polysaccharide molecule is long and has repeating units it binds to lots of BCR on the same cell and drive cross-linking.
One molecule will be recognised by lots of different receptors and pulled into the same space = clustering of Ig provides a signal strong enough for B cell activation
You also need a secondary signal
In T independent antigens, the secondary signal is coming from microbial constituents - PAMPs such as LPS (no need for T helper cells etc)
-> leads to upregulation and release of IgM- no class switching
Q: Explain the activation of B cells via T dependent antigens. What type of antibody is produced?
A: activation by protein based antigen
The antigen has to be taken up by TWO TYPES OF CELL - B cell + Dendritic Cell
BCR recognises the antigen and pulls it into the cell -> the antigen is chopped up and put on the MHC class II - this is what allows APCs to interact with T cells
The loaded MHC class II is presented to a T cell which recognises it through TCR
CRITICAL POINT: B cell and DC both have the same antigen on their MHC class II
The T cell population expands and moves to lymph nodes
In the lymph nodes they bind to the B cell which has the same MHC class II with antigen
THIS PROVIDES THE SECOND SIGNAL
The B cell becomes a plasma cell- can produce all Ig classes
Q: What happens after the T helper cell binds to the antigen on the B cell (complex with MHC class II)? (2)
A: T helper cells secrete lymphokines after recognition of the antigenic/self complex on the surface of the B cell
B cell enters the cell cycle and develops into a clone of cells with identical BCRs
Q: How do cytokines affect Ig classes?
A: There are a number of different types of T helper cells (Th1 and Th2)- These two types of T helper cell are defined by the type of cytokines they produce
The type of cytokine produced by the T h cell has an effect on the type of antibody produced by the B cell- Different cytokines will switch the kind of constant region on the antibody (The variable region remains the same (specificity is the same))
Q: Explain Ig class switch?
A: Once the B cells are in contact with the T cell - the T cell drives the class switching - switch out different exons
B cell changes its DNA so that it produces a different constant region while keeping the variable region
Q: Why is the immune response stronger and faster the second time round? (2) Affinity over time?
A: due to somatic hypermutation and affinity maturation
AID (Activation-Induced Deamination) causes point mutations in the VDJ region which causes small changes in the B cell - evolutionary process
AID - takes the DNA and change the C in GC to an A so that in the next generation you get a T on the opposite strand - these small point mutations cause slight changes in antibody structure.
This is important in improving the antibody response
Affinity improves over time - the antibodies you produce the second time are better than the ones you generate on first exposure
Q: Define affinity maturation.
A: process by which T cell-activated B cells produce antibodies with increased affinity for antigen
Q: Define somatic hypermutation. Seen where?
A: mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching.
*Q: What is an immunological memory a consequence of? Can confer? Basis of?
A: Immunological memory is also a consequence of clonal selection
Can confer lifelong immunity to infections
Basis for vaccines
