6 - B-cell Biology Flashcards
Theory of Clonal Selection
In a group of B-Cells,
a specific antigen only activates its COUNTER-SPECIFIC cell
so that particular cell is
Induced to MULTIPLY for AB production
1 b-cell –> 1 antibody type
Differentiation of B-Cells
In BONE MARROW
- *HSC** (hematopoeitic Stem Cell) –> PRO-Bcell -> PRE-Bcell
- *Immature B-Cell**
in BLOOD
Mature B-Cell
in LYMPHOID TISSUES
Naive B cell –> Plasmoblast (Plasma B-Cells)
or GC-B cell –> Memory B-Cell
–>Bone Marrow / MALT / Spleen as Long-Lived Plasma Cells
Pro-B Cells
HSC -> PRO-B cell in Bone Marrow
COMMITED to becoming B-cells
Heavy-Chain V(D)J Joining occurs
Express:
CD19 & CD34 well surface markers
CD19
Cluster of DIfferentiation
aka Designation or Classification determinant
Expressed on ALL B-CELLS throughout their maturation
important for
Immunophenotyping Cells
PRE-B Cells
Pro-Bcells -> PRE-B cells in Bone Marrow
V(D)J Joining of LIGHT CHAIN
is OCCURING, might not be completed
Producing dominantly IgM, not IgG yet
Expression of:
Pre-BCR on membrane
rearranged u heavy chain w/ surrogate light chain proteins
Immature B Cell
Pre-Bcell -> Immature B Cell, still in Bone Marrow
Recombination of Heavy + Light Chain genes is COMPLETE
either Kappa or Lamda
Now expressing:
Surface IgM as a part of BCR
BCR Signal Transduction
Antigen Binds -> BCR of Immature B-cell
Ig-Alpha / Ig-Beta
conveys message down for signal transduction & amplification
VVV
Effectors that affect cell activity, ex:
MYC / BCL / Cyclins
CENTRAL TOLERANCE
of a Immature B-Cell
Process of ELIMINATING a developing B or T cell
AFTER reacting to self-antigens
Apoptosis
Self-molecule that SHOULDNT be in this AREA –> programmed cell death
Anergy
cell fails to respond to antigen
- *Clonally Ignorant**
- issue w/ signal transduction** –> cell is *NOT activated by atigen
REDO VDJ Recombiation
Brand new BCR is made from old parts –> select a new J-Chain
will still recycle back to central tolerance again
Mature B Cell
Immature B-Cell –> Mature B-Cell in Blood
First only IgM expression –> IgD is also expressed
Alternative Splicing
SAME antigen specificity as the IgM
also forms BCR in association w/ IG-alpha+beta
B-Cell Maturation & Activation
Move from Blood –> SECONDARY LYMPHOID TISSUES
Lymph Nodes / tonsils / spleen / Peyer’s patches / MALT
These organs have Seperate regions for B & T Cells
but will eventually encounter each other
B cells will encounter ANTIGEN & HELPER T-cells
T-Cell Dependent ACTIVATION of B-Cell
- BCR binds antigen
- Particle is taken up through Receptor mediated endocytosis
- degraded & presented to T-cells as pieces in the MHC2 molecules
-
T-Cells recognize & bind MHC2 complex, stimulating T-cell to:
- Produce CD40L –> binds CD40 on B-cell
- Produce CYTOKINES
-
Activated B-cell, will do:
- Proliferate
- SOMATIC HYPERMUTATION
- CLASS SWITCH recombination
Plasma B-Cell Formation
After Activation, via Helper T-Cell + Antigen
VVVV
Enlarge / Proliferate as Plasma B Cells (lymphoBLASTS)
Divide 2-4x a day for 3-5 days
can produce 1000 clones of itself
but can also become:
Memory B Cells
MEMORY B-CELLS
Formed within Germinal Centers
are quiescent & may persist for 10x of years
Express AB on cell surface, BUT do not secrete AB’s
Important in the SECONDARY IMMUNE RESPONSE, for a re-infection
VVVV
Produces Plasma Cells / Effector B-Cells
that procduce Large amounts of the same AB
Long Lived = days to months
Germinal Centers
Where Memory B-Cells are FORMED, following a primary infection
Lymph Nodes & Spleen
Located in the Lymphatic Follicles
Site of
SOMATIC HYPERMUTATION** & **Class Switch Recombination
Dark Zone & Light Zone
Dark Zone of a Germinal Center
Site of SHM = Somatic Hypermutation
Since this is a Random recombination, it can result in:
Recognition of SELF Antigens
VVVV
This is corrected through Perepheral Tolerance
which prevents from causing this isue
