Chapter-6 Flashcards
BC history
- Repertoire assembly
- Neg selec
- Pos selec
- Searching for infection
- Finding infection
- Attacking infec
BC development
- Stem cell- BM of fetal liver
- Early pro- DJ rearrangement
- late pro- v-DJ arrangement
- Late PRE
- Large pRE
- Small Pre
- Immature B cell
BC development
BM storms necessary enviro for be cel devel. Secreted products and coadhesion molecules
VCAM-1
Binds to VLA-4 integrin on early BC progenitor
IL-7
Cytokine important role of
Late pro and late Pre
Stimulate growth and cell division
Ck pts of BC devel
I- VDJ rearrangement gives rise to a functional Pre BC
So then the step before -the late pro BC will be permitted to survive and undergo clinal proliferation
Ck pt 2 in BC dev
Production of LT chain results in a function surface imm and surviva and maturation Of BC
Large Pre B
VDJ rearranged
Late pro b
V-DJ is undergoing re arrangement
Early pro b
D-J rearrangement
Large Pre b
Heavy chain
Small Pre b
Light chain
V-J rearranging
Immature BC
Functional light chain either lambda or kappa
U heavy chain
IgM on surface
After production of heavy chain as a Pre bC (uVDJ)
RAG is degraded
The chromatin struc of heavy chain is reorganized to prevent gene rearrangement
There is allelic exclusion of a second heavy chain
Centrocytes
Somatic hyper mutation has occurred
Isotype switching is complete
Neg selection
Neg selec ensures that auto reactive BC are prohibited from emerging in the body
B cell repertoire is called
Central tolerance when it develops In primary lymphoid organ
Peripheral tolerance
When BC is induced outside the BM
Plasma cell
Differentiates in the medulla and BM
Produces secreted imm instead of the membrane bound form
What is the surrogate light chain I the PRe-BCR ?
VpreB and lambada 5
Pax 5 is analogues to what in the TCD?
Notch 1
What is not possible in Ig heavy chains?
The same attempt in TCD where’re thymocytes can make four attempts to rearrange a b chain this is because in the Ig there is:
Deletion of all non rearranged D segments
In BCD how many attempts does the heavy chain have to rearrange?
Only one attempt of VDJ
BCR summ
Controlled by several genes Somatic recom -Rag Junctional diversity Heavy chain-VDJ first only tries rearrangement twice one on p and one on maternal H chain plus surrogate light chain Apop or success Cell replication if successful Light chain -VJ Tries 4x IgM receptor Apop or success Cell rep if success
Are BC long or short lived?
Are short lived and replenish from immature precursors derived from the BM
What do both B and T cells express?
L-selectin
What is pro BC?
Earliest ID cell of BC lineage
Early pro b does what?
D-j rearrangement
Late pro b rearranges what ?
V-DJ
BM stromal cell func
Cell- cell contact
- VCAM
- SCF to Kit
Secretion of growth factors IL-7
Why can heavy chain locus be inefficient?
Complications through adding of N + P
Alters reading frame
Rearrangement of heavy chain has what efficiency?
D-J arrangement
V-DJ is less ….
Efficient only 50% will make func heavy chain
What does BC need for rearrangement ?
Rag 1&2
BC dev needs upreggulation due to what?
TF = E2A , EBF
If heavy chain is successful then what does that lead to?
U heavy chain
After pro BC then what is next?
Pre BC
Pre BC has what two cells?
Large Pre BC
Small Pre BC
How do we test the surrogate light chain that will be able to combine with light chain?
VpreB
Lamda 5
What is the surrogate light chain controlled by?
TF developed in the BM= E2A, EBF
From formation of Pre BC receptor?
Does Pre BC receptor appear on cell surface yet?
No pt of membrane enclosed vesicle
The formation of Pre b receptor signals what
Pro b to become Pre b
If no Ig a:b cell devel does not what
Progress beyond the progenitor sages
What if lambda 5 def?
Severe BC deficiency
Persistent bacterial infections
Lambda 5 is apart of the surrogate light chain makes Pre B cell receptor unfunctional
Once u chain is assembled the what?
Stops transcription of Rag
Degradation of RAG
Chromatin condensation
Rag is off in BC when..
We have u chain
Rag is off when we have
B chain in the TC
Large Pre b has what
100 small Pre B cell clones
Identical u chain
No longer makes surrogate light chain
Large Pre B cell makes what
Light chain
several attempts of VJ
85% of Pre make successful rearrangement
What does large Pre b not make?
Surrogate light chain
What does functional light chain form with
Assembles with u chain in Er to form IgM
What is a mature BCR
Immature BC
What occurs in small Pre b?
Light chain rearrangement
What is clonal expansion?
One successful heavy chain gene rearrangement leads up to 85 clones of immature bc
What are the two ck pts in BC
1st= late pro, Pre b receptor= heavy chain
2nd= small Pre b=func light chain
What proteins are involved in BC development
TF
GF
Signal transduction
Differentiation markers
Where is Tdt found active at
Heavy chains
What is func of Tdt
Insert N + P
Tdt is only present in
Lymphocytes
Proteins involved in BC development
Tdt
Iga:b until an effector cell
TF of BC development
E2A
EBF
Pax5
PAx 5
The guardian of BC identity and function
Pax 5 is import for the
Commitment of progenitor cell to b lymphocyte
What does pax 5 facilitate
Pre B cell receptor
What does pax 5 induce
V-DJ recombination
What does pax 5 encode
BSAP
What cells are pax 5 in
In all cells
Pax 5 binds to what in early pro b
Enhancer sequence 3’ heavy chain c region
What does pax 5 open up
Chromatin acess to TF= rag
Wht does b1 express
Cd5
What is cd5
Glycoproteins marker of TC lineage
B1 cells have no _____Ig
IgD
B1 cells have what ____ig
High affinity for igM
B2 cells have ____Ig
Low affinity of igM
What cytokines does b1 depend on
IL-10
What can B1 serve as?
APC
What body cavities does B1 defend against
Peritoneal , plural cavities
B1 cells are not produced by what_____
BM =B2
When so we need receptor editing
If new BCR doesn’t react with self antigen
If we have BCR and reacts with self antigen then what happens
Receptor editing - light chain gene rearrangement
Why r there mult v-J segments?
Because kappa light chain genes have mult segments
Clonal deletion
Selective death of developing lymphocytes and removal of self reactive receptor
What is anergy
Inactive and un responsive
What do anergic cells make
IgD & IgM
Anergic has what type of regulation
Down reg of surface igM expression
After BC leaves BM what is expressed on surface
High levels if IgM low IgD
Not fully mature
The final stage of BC develop is where
Secondary lymphoid tiss
Homing is for what
Migration of BC to secondary lymphoid
Summary of self reactive BC
Receptor editing
Die by apop
Become anergic
Central tolerance
Tolerance in primary lymphoid organ
Peripheral tolerance
Apop
Anergy
Kicked out of bone marrow
CCL21 is secreted by
Stromal cells & DC
What is the BCR for CCL21
CCR7
What is CCL19 secreted by
DC
Homing in BC are mediated via
CCL21&19
FDC is not a
APC
What does FDC secrete for homing BC to secondary lymph tiss
CXCL13
What does CXCL13 attract
B cell to follicular DC=FDC
And binds to CXCR5
What preserves integrity of FDC
LT=lymphotoxin
W is LT=lymphotoxin
Surface protein on BC
Binds to receptor on FDC
W is maturation of BC
In 2 lymph
BAFF
BC activation factor
What does BAFF do
Promotes BC survival
Bound by baff receptor
Produced by several cell types
If no antigen then what
BC detached from FDC
Leaves lymph via efferent
Mature naive BC
W d immature BC compete with
Mature BC for acess to FDC
If no acess to FDC then what happens to BC
Death
Favors mature BC
1/2 life of mature BC 100 d if not activated
What does the mature naive BC diff into
Centrolblasts
Dark zone is where
Germinal center
What happens in germinal center
Called dark zone b/c somatic hyper mutation =BC proliferation
Then what do centroblasts diff into
Centrocytes
Centrocytes migrate w
Into light area
Into light area by w
Chemokine:
Helper TC
FDC
W is T of centrocytes
Somatic hypermutatio
Isotype switching is complete
What does FDC present
Present antigen on surface
Compete for survival
W r fates of centrocytes
Apop
Class switching
Plasma cell
Memory cell
W do plasma cell migrate
To medullary cords in lymph
Red pulp in spleen
Laminate propia in gut
BM
Memory cells do w
Recirculate for long peroid
Require some stim from FDC
Are predom igG
What Ig is memory BC
IgG had already undergone class switching
Explain briefly how movement if BC into LN
Entry via HEV through afferent vessel
Migrated into a follicle : CCCR5 -CXCL13
Migrates thru FDC
The. Is yes or n for antigen encounter
Migrates thru FDC
Then Is yes _____
Travels through the TC zone in germinal center to make then a centrocytes which can have various fates
n for antigen encounter _____
The cell exits via efferent vessel