Immunology 5: B Lymphocytes Flashcards
What do the absence of T and B cells cause
Severe Combined Immune Deficiency (SCID)
Where do B cells come from?
B cell generation and maturation occurs in bone marrow in the absence of antigen
They migrate into the circulation and into lymphoid tissues
Each B cells will recognise a specific antigen
Specificity resides in the BCR (B Cell Receptor) - this is a membrane-anchored antibody
key difference between T cells and B cells in the TYPE OF EPITOPE they recognise:
T cells - identify the sequence
B cells - identify the structure (tertiary)
What is the epitope
the region of an antigen that the antibody binds to
What does the B-cell receptor look like
The B cell receptor is an antibody that is bound to a couple of transmembrane domains which transduce the signal.
What does the BCR consist of
membrane-anchored antibody and di-sulphite linked heterodimers Iga and Igb
What are the roles of the Igalpha and IgBeta hetrodimers
The cytoplasmic tails of Iga/Igb is long enough to interact with intracellular signalling molecules
When the BCR recognises an antigen, there is a structural change which drives signalling via Iga/Igb
How are antigen receptors produced
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
This is called IMMUNOGLOBULIN GENE REARRANGEMENT
This generates the diversity of the lymphocyte repertoire
Describe the Expression of an Immunoglobulin Light Chain
There are 70 variable units that people have - 40 in kappa and 30 in lambda
The 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 Variable and Joining regions (this is random)
So then the B cell has a variant version of this gene.
Different splicing patterns give rise to further variation
What enzyme enables DNA recombination
V(D)J Recombinase
Encoded by RAG genes
Deficiency leads to SCID
How many segments do heavy chains have?
3
WHich chain goes under rearrangement first
Heavy
What happens when the B cell bind with antigens and transduces a signal through BCR?
Starts as a naïve B cell
It is stimulated by antigens and interacts with T cells
It will go into lymph nodes (B cell areas)
What are the 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
Where do the acessory signal for b cells come from
Directly from microbial constituents
T helper cell
How is antibody production by B cells achieved?
T cell dependent T helper cell Broader family Protein based antigens All Ig classes
T cell independent
ONLY IgM
Recognise microbial constituents
Associated with polysaccharide
Describe the process of making T Independent Antigens
Main thing it’s related to is polysaccharides
The polysaccharide has a repeating subunit
Because the molecule is long and repeating 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.
You also need a secondary signal
In T independent antigens, the secondary signal is coming from microbial constituents - PAMPs such as LPS
Describe the process of making T Dependent Antigens
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
Once it has been pulled 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
What happens after the T helper cell binds to the antigen?
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
Cytokines influence Ig classes
There are a number of different types of T helper cells defined by the type of cytokines they produce
Different cytokines will switch the kind of constant region on the antibody
The variable region remains the same (specificity is the same)
The type of T cell that the B cell is exposed to is critical in how the antibodies respond
Ig Class Switch
Once the B cells are in contact with the T cell - the T cell drives the class switching
You keep the variable region and you switch out different exons to give you a different constant region.
Different effect
What is Somatic Hypermutation and Affinity Maturation
AID (Activation-Induced Deamination) causes point mutations in the VDJ region which causes small changes in the B cell
It is an 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.
Best binding antibody producing b-cell survives the rest die
What is Immunological Memory
Immunological memory is also a consequence of clonal selection
Can confer lifelong immunity to infections
Basis for vaccines
Affinity - the ability of the antibody to bind to an antigen
Affinity improves over time - the antibodies you produce the second time are better than the ones you generate on first exposure
When B cells go bad
Antibodies play a role in a number of autoimmune diseases e.g. Myasethenia gravis
IgE is involved in anaphylaxis
Some B cells can turn into cancers (lymphomas and myelomas) especially under the influence of viruses e.g. Epstein-Barr Virus
