Lecture 13 Flashcards
(26 cards)
What are the goals of B Lymphocyte Development? (3)
- generate diverse antigen receptors
- alter/eliminate self-reactive B cells / BCRs
- promote foreign reactive B cells to become mature B cells in the secondary lymphoid organs.
Where does b cell development occur? (not specific – think broadly)
bone marrow
in what component of bone marrow does b cell development occur? what happens (physically)?
- Mesenchymal stromal cells
- developing b cell attatches to the cell through adhesion molecules, and receives growth factors.
What are the stages of B cell development, in order? (8)
- stem cell
- early pro-B cell
- late pro-B cell
- large pre-B cell
- small pre-B cell
- immature B cell
- transitional B cell
- mature B cell
What transcription factors are important for B cell devlopment in order of occurance? (4)
- E2A
- FOX01 / EBF
- PAX5
(these all play a role in developing the early pro-B cell)
When does D-J (heavy chain) rearrangement occur in b cell development?
early pro-B cell
True or False?
D-J (heavy chain) rearrangement in B cell development occurs on both chromosomes at the same time?
true
When does V-DJ (heavy chain) rearrangement occur in B cell development?
late pro-B cell
True or False?
V-DJ (heavy chain) rearrangement in B cell development occurs on both chromosomes at the same time.
False.
(it happens one at a time – a failure in one signals cell death)
What checkpoint occurs in the large pre-B cell?
formation of the pre-BCR
What does the pre-BCR do?
- it pairs the completed heavy chain with a surrogate light chain.
- allows progression to light chain rearrangement.
- Tests the functionailty of VDJ (heavy chain) functionality.
what is allelic exclusion when refering to b cell devlopment?
formation of the pre-BCR tests the VDJ(h). If it finds one of the VDJ(h) on a chromosome to be functional, it signals for the other to inhibit further rearrangement.
When does V-J (light chain) rearrangement occur in B cell development?
small pre-B cell
What checkpoint occurs in the immature B-cell?
central tolerance
(negative selection 1)
what is the purpose of central tolerance in B cell development?
- tests if VDJ (light chain) works with the heavy chain
- insures no self-reactivity and allelic/isotypic exclusion using antigens in the stroma and soluable molecules.
what happens if a cell is found to be self-reactive during the central tolerance.
it goes back for receptor editing (changes to receptor specificity)
What checkpoint occurs in the transitional b cell?
peripheral tolerance
(negative selection 2)
what is the purpose of central tolerance in B cell development?
- tests if b cells can identify new antigens in periphery using antigens expressed by spleenocytes and soluble molecules.
what happens if a cell is found to be non-reactive during the peripheral tolerance.
apoptosis (no receptor editing – only death).
What is the order of L chain rearrangemtn in B cell development?
- Lκ on chromosome 1
- Lκ on chromosome 2
- Lλ on chromosome 1
- Lλ on chromosome 2
After an immature B cell is made, it’s exported to the ____ to complete its maturation.
spleen
An immature B cell is made up on which antibody(s)?
IgM
A mature B cell us made up on which antibody(s)?
IgM and IgD
In the spleen, B cells become one of two types of transitional b cells. What are they? How are they different?
T1B: high IgM, no IgD, low CD21 (+BAFF-R)
T2B: high IgM, high IgD, high CD21(+BAFF-R)
- follicular dendritic cells express BAFF. BAFF stimulates BAFF-R on T1B for survival.
