Basics of B-cells Flashcards
What are B-cells?
B-cells are a cell of the adaptive immune system, functioning in antibody production and as antigen presenting cells
What are immunoglobulins?
Antibodies - Antigen specific proteins, produced by B cells and plasma cells
Describe the composition of an antibody
They are a complex of 4 polypeptide chains; 2 heavy chains and 2 light chains
What are the 5 types of antibody?
- IgM - Mu heavy chain
- IgG - Gamma heavy chain
- IgA - Alpha heavy chain
- IgE - Epsilon heavy chain
- IgD - Delta heavy chain
What are the 2 types of light chain?
Kappa
Lambda
What are the 5 types of heavy chain?
Mu
Gamma
Alpha
Epsilon
Delta
Where does initial antibody production occur?
In the bone marrow under the control of the microenvironment
What region of an antibody binds to antigens?
Variable region
What are the 3 main parts of the antibody variable region?
Variable
Diversity
Joining
How does the body produce millions of types of antibodies specific to different antigens?
There are millions of combinations of VDJ segments
What are the 2 types of immunoglobulin production?
Polyclonal
Monoclonal
What is the normal type of immunoglobulin production?
Polyclonal
What is meant by polyclonal immunoglobulin production?
The immunoglobulin array is produced by many different plasma cell clones
What are some stimuli of polyclonal immunoglobulin production?
Infection
Autoimmunity
Malignancy
Liver disease
What is monoclonal immunoglobulin production a marker of?
Underlying B-cell or plasma cell disorders
What is meant by monoclonal immunoglobulin production?
This involves the immunoglobulin array being produced by a single B-cell which has undergone clonal expansion and must have prevented all others from dividing
This results in the production of identical antibodies, known as paraproteins, with the same structure and specificity
What are paraproteins?
These are identical copies of the same antibody, produced by the same clonal B-cell
How are types of immunoglobulin detected?
Serum electrophoresis
How does serum electrophoresis work?
Immunoglobulins are detected by serum electrophoresis, in which a voltage is applied across a gel with the serum sample
The separated serum proteins appear as distinct bands or zones
This is then classified against a known result
What are some causes of paraprotein formation?
- MGUS
- Myeloma
- Amyloidosis
- Lymphoma
- Solitary or extra-medullary plasmacytoma
- CLL
- Waldenstroms macroglobulinaemia
What is meant by somatic hypermutation?
This is the production of many B-cells with a huge number of mutations in production of antibodies
Those with high affinity for antigens survive and proliferate, while those with poor affinity undergo apoptosis
This is somatic so only affects the VDJ segments and doesn’t affect germ-line DNA, so is not passed on
What are some histological features of plasma cells?
- Eccentric “Clock face nucleus” on H&E staining
- Open chromatin (Synthesising mRNA)
- Plentiful blue cytoplasm with lots of protein
- Pale perinuclear area due to golgi apparatus
What are Bence-Jones proteins?
These were proteins found in warming the urine of patients with bone pain and oedema in the 1800s
This was later confirmed to be immunoglobulin light chains
What causes the presence of Bence-Jones proteins in the urine?
When immunoglobulins are synthesised in plasma cells, excess light chains are formed which are secreted into the plasma
In cases of increased immunoglobulin synthesis, more moves into the blood and so is excreted into the urine