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