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Immunology
18- B cell Development
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B Cell
Arise in bone marrow then finish development in spleen
Only cell that produces immunoglobulins
Activates by binding antigen and signal transduction
Life cycle of B cell
1.
Early Pro-B
2.
Late Pro-B
3.
Pre-B
4.
Immature B
Early Pro-B
DJ heavy chain recombination
Start of
V-DJ H chain recombination
Late Pro-B
DJ heavy chain
Pre-B
Heavy
chain expressed as
pre-BCR
Lots of
cell division-
goes from
large pre to small pre
VJ light chain recombination
Make sure that the
heavy chain
works with
pre-B light chain
Immature B
IgM surface receptor expression
Negative selection (Deletion if bound to light, receptor edition)
Cytokines involved
IL-7
,
CD19
B Cell Development in Bone Marrow
1.
HSC
circulates in blood then makes contact with
CXCL12
to become
pre-pro B cells
2. Then contact
IL-7
: when
Pro-B cells
then progress through
Pre-B
to
immature B stages
Immature B Cells
Proper IgM
on cell surface with
Iga
and
IgB
Exposed to
self antigens
: if it bonds,
negative selection
(
apoptosis
)
Becoming Mature B cells
1. 2 transitional stages (T1:
low IgD expression
, T2:
intermediate IgD expression
)
2. Then go through
positive
and
negative selection
3.
BAFF
makes sure IgD can pass a
viable signal
Mature B cells
Fully functional
and ready to circulate
If in periphery and react to self:
Apoptosis
or
Anergy
(inavation)
B Cells to peripheral Sites
Lymph node chemokines bring dendritic cells and B cells in and out with gradients
Process of B-cell Second Signal
1.
T dependent
: Need a helper T cell in the lymph node (
CD40/CD40L
)
2.
T Independents
: not cell involved (Engage
B cell receptor
and
PRRs
, Engage
B cell receptor
and
CD21
(
complement
) with
C3d
)
Somatic hyper mutation
/
affinity maturation
improves
antigen binding dramatically
Apoptosis Intrinsic Pathway
Stress
,
radiation
,
remove growth factors
Signalling through TCR
with
no second signal
Strong TCR signals during development
Apoptosis
Extrinsic Pathway
Caused by
membrane receptors
engaging
extracellular ligands
Apoptosis
Activates caspases