B cell Diversity Flashcards
(46 cards)
Where are B cell first made?
Liver of foetus at 8-9 weeks
What variation of light chains are there?
Lambda and Kappa
How many constant regions are there in the LC and HC?
4-5 in lambda
1 in kappa
9 in HC
Which chain has the D gene segment in B cells?
Heavy chain
What happens in heavy chain recombination?
DJ recombine first
Then V recombines with DJ
What is needed to recognize antigens?
Mostly, HC and LC are required
Exception = some antibodies can recognize with only HC or HL (only 3CDRs needed)
This means it doesn’t matter what the other chain is
What cells do B cell development go through?
Haematopoietic stem cells
MPP
CLP
Pre-B
B cell
How do B cell develop?
MPP recognize FLT3 ligand with FLT3R
Causes differentiation into CLP
VLA4 binds VCAM1 together with IL-7 commits CLP into early pro-B cell lineage = HC DJ recombination giving a late pro-B cell
V recombining with DJ = pre-B cell
VJ recombination of light chain occur in pre-B cell and Ig expressed intracellularly
Immature B cell has Ig expressed on cell surface
Where is FLT3 ligand found?
Bone marrow of stromal cells
What receptor is found in bone marrow stromal cells that CLP binds to?
VCAM1 found on the bone marrow stromal cell
It is bound by VLA4
What chain performs repeated rearrangements?
Light chain loci
How to eliminate autoreactive B and T cells?
T cell = positive and negative selection
B cells = peripheral and central tolerance
Where does central tolerance happen?
Bone marrow
What is positive selection and why does this not happen for antibodies?
This is selecting for cells that recognize your own MHC
Antibodies don’t need to recognize MHC
What is a mature B cell?
Fully VDJ recombined
Light and heavy chain are paired
What happens to immature B cells that have no self reaction? [central tolerance]
Migrate to the periphery to become a mature B cell
What happens to immature B cells that have multivalent self reaction? [central tolerance]
Clonal deletion or receptor editing
Receptor editing only happens in B cells in the bone marrow
What happens to immature B cells that react to soluble self molecules? [central tolerance]
Migrate to the periphery and become anergic B cells
What are anergic B cells?
Cells that persist in the periphery but are unresponsive to antigen
What happens to immature B cells that have low-affinity to self? [central tolerance]
Migrate to periphery to become mature B cell
Clonally ignorant though, don’t bind antigen???
What happens in receptor editing?
B cell development stops and rearrangement of LIGHT CHAIN
New receptor specificity is not expressed
What happens to immature B cells that have no self reaction? [peripheral tolerance]
Becomes mature B cells
What happens to immature B cells that react to multivalent self molecules? [peripheral tolerance]
Apoptosis = NO receptor editing
What happens to immature B cells that react to soluble self molecules? [peripheral tolerance]
Anergic B cell»_space;> Apoptosis
