Lecture 17 - Lymphocyte Development - B Cells Flashcards
Where do B cells mature in birds?
Bursa of fabricus
Where do B cells mature in humans?
Bone marrow
State of BCR in an immature B cell
Fully mature BCR
Why are there fewer BCR expressed than possible gene rearrangements?
V(D)J recombination is not completely random, hence why there are ~10^6 expressed BCR, and 10^11 theoretical combinations of V(D)J genes
From what do all lymphocytes arise?
Uncommitted progenitors
Granulocytes arising from granulocyte myeloid progenitor 1) 2) 3) 4) 5)
1) Neutrophil
2) Eosinophil
3) Basophil
4) Monocyte
5) Unknown mast cell precursor
Is the multipotent progenitor self-renewing?
No
Function of stromal cells
Secretes factor essential for B cell maturation
Stromal cell location
Bone marrow
Where in the bone marrow is the multipotent progenitor?
Endosteum
How is B cell development location-dependent?
Stromal cells secrete different factors required for B cell development in different places in the bone marrow.
B cells become more mature as they move from the endosteum into the central sinus
When is the heavy mu chain produced?
Recombined in pre-pro and pro B cells
Expressed on pre-B cells
Pre-B cells that don’t produce mu chains die
What induces surrogate light chain assembly?
E2A-induced lambda 5
Components of the surrogate light chain
VpraB, Igalpha, Igbeta, SLC
How does signalling through the pre-BCR occur?
Pre-BCR dimerisation/oligomerisation
Important enzyme in pre-BCR signalling
Bruton’s tyrosine kinase
Interleukin that is essential for B cell development
IL-7
What happens at the conclusion of heavy-chain rearrangement?
Pre-b cell large expands 30-60-fold before transitioning to resting pre-B cell small
Consequence of expansion of pre-B cell large before transitioning to small
Large number of pre-B cell small with identical heavy chains
What is a B cell only being able to express kappa or lamba light chain called?
Isotypic exclusion
What happens in the transition between pre-B cell small and immature B cell?
IgM is expressed
Is antigen needed for pre-BCR to be engaged?
No
Number of attempts at heavy chain recombination
Two
Because of allelic exclusion
Number of attempts at light chain recombination
Four
Because of allelic exclusion and kappa and lambda loci
When does Bruton’s X-linked agammaglobulinaemia present?
~3 months after birth
RAG expression during B cell development
Two peaks
1) Early pro-B cell
2) Pre-B cell
What ensures that a B cell can only make one type of antibody?
Allelic exclusion
Negative selection/Clonal deletion
If an immature B cell encounters a strongly-cross-linking antigen in the bone marrow
Only self antigens should be in the bone marrow
What can save an immature B cell from clonal deletion?
RAG is still active at the stage of immature B cell, and can initiate receptor editing
Stages of B cell development where heavy chain locus is rearranged
Early, late pro-B
Stage of Bc ell development where light chain locus is rearranged
Pre-B
Signals without which immature B cells will die
Positive signals
