Chapter-6 Flashcards
(121 cards)
1
Q
BC history
A
- Repertoire assembly
- Neg selec
- Pos selec
- Searching for infection
- Finding infection
- Attacking infec
2
Q
BC development
A
- Stem cell- BM of fetal liver
- Early pro- DJ rearrangement
- late pro- v-DJ arrangement
- Late PRE
- Large pRE
- Small Pre
- Immature B cell
3
Q
BC development
A
BM storms necessary enviro for be cel devel. Secreted products and coadhesion molecules
4
Q
VCAM-1
A
Binds to VLA-4 integrin on early BC progenitor
5
Q
IL-7
A
Cytokine important role of
Late pro and late Pre
Stimulate growth and cell division
6
Q
Ck pts of BC devel
A
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
7
Q
Ck pt 2 in BC dev
A
Production of LT chain results in a function surface imm and surviva and maturation Of BC
8
Q
Large Pre B
A
VDJ rearranged
9
Q
Late pro b
A
V-DJ is undergoing re arrangement
10
Q
Early pro b
A
D-J rearrangement
11
Q
Large Pre b
A
Heavy chain
12
Q
Small Pre b
A
Light chain
V-J rearranging
13
Q
Immature BC
A
Functional light chain either lambda or kappa
U heavy chain
IgM on surface
14
Q
After production of heavy chain as a Pre bC (uVDJ)
A
RAG is degraded
The chromatin struc of heavy chain is reorganized to prevent gene rearrangement
There is allelic exclusion of a second heavy chain
15
Q
Centrocytes
A
Somatic hyper mutation has occurred
Isotype switching is complete
16
Q
Neg selection
A
Neg selec ensures that auto reactive BC are prohibited from emerging in the body
17
Q
B cell repertoire is called
A
Central tolerance when it develops In primary lymphoid organ
18
Q
Peripheral tolerance
A
When BC is induced outside the BM
19
Q
Plasma cell
A
Differentiates in the medulla and BM
Produces secreted imm instead of the membrane bound form
20
Q
What is the surrogate light chain I the PRe-BCR ?
A
VpreB and lambada 5
21
Q
Pax 5 is analogues to what in the TCD?
A
Notch 1
22
Q
What is not possible in Ig heavy chains?
A
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
23
Q
In BCD how many attempts does the heavy chain have to rearrange?
A
Only one attempt of VDJ
24
Q
BCR summ
A
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
25
Are BC long or short lived?
Are short lived and replenish from immature precursors derived from the BM
26
What do both B and T cells express?
L-selectin
27
What is pro BC?
Earliest ID cell of BC lineage
28
Early pro b does what?
D-j rearrangement
29
Late pro b rearranges what ?
V-DJ
30
BM stromal cell func
Cell- cell contact
- VCAM
- SCF to Kit
Secretion of growth factors IL-7
31
Why can heavy chain locus be inefficient?
Complications through adding of N + P
Alters reading frame
32
Rearrangement of heavy chain has what efficiency?
D-J arrangement
33
V-DJ is less ....
Efficient only 50% will make func heavy chain
34
What does BC need for rearrangement ?
Rag 1&2
35
BC dev needs upreggulation due to what?
TF = E2A , EBF
36
If heavy chain is successful then what does that lead to?
U heavy chain
37
After pro BC then what is next?
Pre BC
38
Pre BC has what two cells?
Large Pre BC
| Small Pre BC
39
How do we test the surrogate light chain that will be able to combine with light chain?
VpreB
| Lamda 5
40
What is the surrogate light chain controlled by?
TF developed in the BM= E2A, EBF
From formation of Pre BC receptor?
41
Does Pre BC receptor appear on cell surface yet?
No pt of membrane enclosed vesicle
42
The formation of Pre b receptor signals what
Pro b to become Pre b
43
If no Ig a:b cell devel does not what
Progress beyond the progenitor sages
44
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
45
Once u chain is assembled the what?
Stops transcription of Rag
Degradation of RAG
Chromatin condensation
46
Rag is off in BC when..
We have u chain
47
Rag is off when we have
B chain in the TC
48
Large Pre b has what
100 small Pre B cell clones
Identical u chain
No longer makes surrogate light chain
49
Large Pre B cell makes what
Light chain
several attempts of VJ
85% of Pre make successful rearrangement
50
What does large Pre b not make?
Surrogate light chain
51
What does functional light chain form with
Assembles with u chain in Er to form IgM
52
What is a mature BCR
Immature BC
53
What occurs in small Pre b?
Light chain rearrangement
54
What is clonal expansion?
One successful heavy chain gene rearrangement leads up to 85 clones of immature bc
55
What are the two ck pts in BC
1st= late pro, Pre b receptor= heavy chain
2nd= small Pre b=func light chain
56
What proteins are involved in BC development
TF
GF
Signal transduction
Differentiation markers
57
Where is Tdt found active at
Heavy chains
58
What is func of Tdt
Insert N + P
59
Tdt is only present in
Lymphocytes
60
Proteins involved in BC development
Tdt
| Iga:b until an effector cell
61
TF of BC development
E2A
EBF
Pax5
62
PAx 5
The guardian of BC identity and function
63
Pax 5 is import for the
Commitment of progenitor cell to b lymphocyte
64
What does pax 5 facilitate
Pre B cell receptor
65
What does pax 5 induce
V-DJ recombination
66
What does pax 5 encode
BSAP
67
What cells are pax 5 in
In all cells
68
Pax 5 binds to what in early pro b
Enhancer sequence 3' heavy chain c region
69
What does pax 5 open up
Chromatin acess to TF= rag
70
Wht does b1 express
Cd5
71
What is cd5
Glycoproteins marker of TC lineage
72
B1 cells have no _____Ig
IgD
73
B1 cells have what ____ig
High affinity for igM
74
B2 cells have ____Ig
Low affinity of igM
75
What cytokines does b1 depend on
IL-10
76
What can B1 serve as?
APC
77
What body cavities does B1 defend against
Peritoneal , plural cavities
78
B1 cells are not produced by what_____
BM =B2
79
When so we need receptor editing
If new BCR doesn't react with self antigen
80
If we have BCR and reacts with self antigen then what happens
Receptor editing - light chain gene rearrangement
81
Why r there mult v-J segments?
Because kappa light chain genes have mult segments
82
Clonal deletion
Selective death of developing lymphocytes and removal of self reactive receptor
83
What is anergy
Inactive and un responsive
84
What do anergic cells make
IgD & IgM
85
Anergic has what type of regulation
Down reg of surface igM expression
86
After BC leaves BM what is expressed on surface
High levels if IgM low IgD
Not fully mature
87
The final stage of BC develop is where
Secondary lymphoid tiss
88
Homing is for what
Migration of BC to secondary lymphoid
89
Summary of self reactive BC
Receptor editing
Die by apop
Become anergic
90
Central tolerance
Tolerance in primary lymphoid organ
91
Peripheral tolerance
Apop
Anergy
Kicked out of bone marrow
92
CCL21 is secreted by
Stromal cells & DC
93
What is the BCR for CCL21
CCR7
94
What is CCL19 secreted by
DC
95
Homing in BC are mediated via
CCL21&19
96
FDC is not a
APC
97
What does FDC secrete for homing BC to secondary lymph tiss
CXCL13
98
What does CXCL13 attract
B cell to follicular DC=FDC
And binds to CXCR5
99
What preserves integrity of FDC
LT=lymphotoxin
100
W is LT=lymphotoxin
Surface protein on BC
Binds to receptor on FDC
101
W is maturation of BC
In 2 lymph
102
BAFF
BC activation factor
103
What does BAFF do
Promotes BC survival
Bound by baff receptor
Produced by several cell types
104
If no antigen then what
BC detached from FDC
Leaves lymph via efferent
Mature naive BC
105
W d immature BC compete with
Mature BC for acess to FDC
106
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
107
What does the mature naive BC diff into
Centrolblasts
108
Dark zone is where
Germinal center
109
What happens in germinal center
Called dark zone b/c somatic hyper mutation =BC proliferation
110
Then what do centroblasts diff into
Centrocytes
111
Centrocytes migrate w
Into light area
112
Into light area by w
Chemokine:
Helper TC
FDC
113
W is T of centrocytes
Somatic hypermutatio
| Isotype switching is complete
114
What does FDC present
Present antigen on surface
Compete for survival
115
W r fates of centrocytes
Apop
Class switching
Plasma cell
Memory cell
116
W do plasma cell migrate
To medullary cords in lymph
Red pulp in spleen
Laminate propia in gut
BM
117
Memory cells do w
Recirculate for long peroid
Require some stim from FDC
Are predom igG
118
What Ig is memory BC
IgG had already undergone class switching
119
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
120
Migrates thru FDC
| Then Is yes _____
Travels through the TC zone in germinal center to make then a centrocytes which can have various fates
121
n for antigen encounter _____
The cell exits via efferent vessel
