B-lymphocytes Flashcards
What is the difference between B and T?
- type of epitome they recognize
- T cells identify sequence (primary structure)
B cells identify structure
What is the lifecycle of a B cell?
- generation and maturation in bone marrow in absence of antigen
- Migrate into circulation and lymphoid tissue
- Each B cell specific to antigen (BCR)
- Self specific receptors removed early on in development as result of clonal selection
What is the structure of the BCR?
- Antibody bound to a couple of transmembrane protein complex
- Have unique binding site for epitope
- Has disulphide linked heterodimers IgA and IgB which have Ig like folds
- Cytoplasmic tails of mIg too short to signal but IgA/B long enough to interact with intracellular signaling molecules
- When BCR recognizes antigen causes structural change driving signaling via IgA/B
Where is the BCR encoded?
- By separate multigene families on different chromosomes
How is the light chain expressed?
- Exist in genomic DNA as cluster
- as B cells develop get rid of most variable units leaving a 2 V and 1 J regions
What is the structure of the light and heavy chain?
- Light chain V+J
- Heavy chain V+J(a couple)+D
What is the role of VD(J) recombinase?
- enzyme complex encoded by RAG gene
- Unused DNA looped out
What are the 3 possible pathway once a B cell recognizes an antigen?
- Affinity maturation: antibody response improves
- Memory cell
- Plasma cell
- Naive antigen specific lymphocyte can’t be activated by antigen along
- Requires co stimulation from T helper cells or microbial constituents
What are the pathways of antibody production?
- T cell independent: only IgM
- Activate without T cell
- Also needs secondary signals from microbial constituents
- Related to polysaccharides, sugar needs repeating structure - T cell dependent antigens: all Ig classes (memory)
- antigen has to be taken up by B cell and dendritic cell
- Expressed to T cell
What happens during Ig Class switch?
- once B cells in contact with T cell drives class switching
- Switch out different exons to give different constant regions
- different cytokines switch kind of constant region on body
- produces the different classes of antibody but does not affect antibody specificity.
What is somatic hypermutation and affinity maturation?
- Improved secondary response
- Activation induced deamination (AID): point mutation in VDJ region deliberately induced gives small change in B cell
- Evolutionary process causing slight change in antibody structure
How many chromosomes are in charge of gene rearragnemnt?
3
One is responsible for kappa light chains, one for lambda light chains and one for all the heavy chains.
What are the steps in T cell dependent activation?
- The membrane bound BCR recognises antigen
- The receptor-bound antigen is internalised and degraded into peptides
- Peptides associate with “self” molecules (MHC class II) and is expressed at the cell surface
- This complex is recognised by matched CD4 T helper cell and the B cell activated
How many chromosomes are involved in Ig chain coding?
3, kappa, lambda, heavy
How is DNA for the variable and constant region stored?
- The genes coding for the variable regions are stored together upstream of the genes for the constant region.
- not necessary to repeat the constant region DNA for each different variable region.
What occurs during gene rearrangement in the light chain?
- one of the V segments comes together with one of the J segments
- Unwanted DNA is looped out by a special mechanism
- primary RNA transcript consisting of VJ linked to the constant region© produced
- Unwanted RNA between J and C is spliced out to give mRNA for VJC.
- translated into the light chain.
What occurs during gene rearrangement in the heavy chain?
similar for lambda light chains and the heavy chains, but for the heavy chains there is a series of D segments between the V and J segments and the mRNA thus represents VDJC.
