Chapter 6: The Development Of B Lymphocytes Flashcards
1
Q
B cells are important players in…
A
- adaptive immunity
2
Q
Stem Cells
A
- give rise to immune stem cells in bone marrow
3
Q
Lymphoid Progenitor Cells
A
- give rise to T and B lymphocytes
- they are the cornerstones of the immune system
4
Q
B Lymphocytes
A
- start developing in the bone marrow
- mature B-cells produce specific antibodies against foreign aantigen
5
Q
T Lymphocytes
A
- leave bone marrow and migrate to the thymus where they mature
6
Q
Phase 1 of B cell development
A
- generation of diverse and clonally expressed B-cell receptors in the bone marrow
- repertoire assembly
7
Q
Phase 2 of B-cell Development
A
- alteration, elimination or inactivation of B-cell receptors that bind to the components of the human body
- Negative selection
8
Q
Phase 3 of B-cell Development
A
- promotion of a faction of immature B cells to become mature B cells in the secondary lymphoid tissues
- Positive selection
9
Q
Phase 4 of B-cell development
A
- recirculation of mature B cells between lymph, blood, and secondary lymphoid tissues
- Searching for infection
10
Q
Phase 5 of B-cell Development
A
- activation and clonal expansion of B cells by pathogen-derived antigens in secondary lymphoid tissues
- finding infection
11
Q
Phase 6 of B-cell Development
A
- differentiation to antibody-secreting plasma cells and memory B cells in secondary lymphoid tissue
- Attacking infection
12
Q
B-cell development is stimulated by…
A
- bone marrow stromal cells
13
Q
Stromal cells are needed to…
A
- provide the microenvironment for the various stages of maturation of hematopoietic stem cells
14
Q
B-cells develop in the BM and then go….
A
- migrate to the secondary lymphoid tissues (spleen, lymph nodes, peyer’s patches, etc.)
15
Q
Pro-B cells develop…
A
- from pluripotent hemapoietic stem cells
16
Q
Protein Markers on the cell surface…
A
- identify the cells at their different stages
17
Q
The different stages in b-cell maturation are correlated with…
A
- molecular changes that accompany the gene rearrangement
18
Q
Which chain genes are rearranged first?
A
- heavy-chain of IgM
- produces a functional step that allows the cell to proceed to the next stage
19
Q
Heavy-chain gene…
A
- regulates the progression of gene rearrangement (feedback regulation)
20
Q
Pro-B cell rearrangement of the heavy-chain locus is…
A
- inefficient
- at each rearrangement event there is only 1 in 3 chance of the correct reading frame being maintained
21
Q
Immunoglobulin heavy chain gene rearrangement in pro-b cells give rise to both ___________ and ______________ rearrangements.
A
- productive
- nonproductive
22
Q
A productive rearrangement…
A
- enables the B cell to proceed to the next stage of development
- rearrangements occur at the H-chain genes on both chromosomes, and if neither is successful the cell dies
23
Q
The large Pre-B cell receptor monitors…
A
- the quality of immunoglobulin heavy chains
24
Q
If you cant make the heavy u chain, then…
A
- apoptosis is triggered
25
Even if you could make the heavy chain, you got to get along with the pseudo-light chain (surrogate LC) which are made...
- VpreB and (lambda)5 polypeptides
26
The pre-B receptor is distinguished from the B-cell receptor in that it lacks an immunoglobulin light chain, which is replaced by the ________________________.
- surrogate light chain made up from the VpreB and (lambda)5 polypeptides
27
It is thought that the pre-B cell receptor does not appear on the cell surface but ________ ______ ______ _____ in the cytoplasm, as part of membrane-closed vesicles.
- remains inside the cell
28
Pre-Be cell receptor causes allelic exclusion
- prevents B cells from making more than one functional heavy (mu) chain
29
Allelic Exclusion at the Ig loci results in B cells w/ antigen receptors of a _______ specificty
- single
30
LC loci rearrangement by small pre-B cell is...
- relatively efficient (2 loci; kappa and lambda)
| - no diversity segment here thus give LC gene rearrangement more chances to get a correct LC (VJ) chain
31
Pre-B cell events leads to the....
- immature B cell that expresses IgM
32
Development of B cells in Bone Marrow
- two checkpoints need to be passed
- both checkpoints are marked by whether a functional receptor is made, which is a test of whether a functional HC (1st cp) or LC (2nd cp) has been produced
- cells that fail die by apoptosis
33
Chromosomal translocations
- B cell tumors carry this that join genes to genes that regulate growth
- as B cells cut, splice, and mutate their Ig genes int he normal events can go awry that converts B cell into a tumor cell
34
Burkitt’s Lymphoma
- breakage of proto-oncogene MYC on chromosome 8 translocates to the Ig gene on chromosome 14 causing no reproduction and is then targeted for apoptosis
35
Which chain genes are rearranged first LC or HC?
- heavy chains are rearranged before LC genes
| - HC must develop before the B cell can proceed to the next stage
36
If nonreproductive arrangement is made on one of the chromosome of a homologous pair, then rearrangement is attempted on the second chromosome.
- re read that again
37
Immature B cells can leave the bone marrow...
- when they dont react with self antigens
| - if the are auto-reactive, they must stay in the bone marrow until they lose their self reactivity
38
Immature B cells w/ specificity for multivalent self antigens are retained in the bone marrow
- NEGATIVE SELECTION
39
Autoreactive modification of B cells
- receptor editing/central tolerance
40
Receptor editing
- changes their antigen specificity
- binding to self antigen in the bone marrow causes the immature B cell to continue to rearrange its LC locus
- this deletes the existing self- reactive rearrangement and may also produce a new LC rearrangement
- if no successful rearrangements are possible, then the B cell dies (apoptosis)
41
Sometimes B cells leave the bone marrow and react against self-antigen, but they become angeric (anergy) unresponsive and eventually die. This is an example of...
- Peripheral tolerance
42
Maturation and survival pf B cells requires access to ____________ _____________.
- lymphoid follicles
43
After they graduate, they still are immature B cells that produce low levels of IgD and high levels of IgM on their surfaces. How do they become mature?
- undergo positive selection
44
Chemokine attracts them to the ____________ lymphoid tissues.
- secondary
45
They move to the Primary Lymphoid Follicles where they mature and become __________ B-cell and produce a bunch of _________ and fewer ______ on their surfaces.
- Mature
- IgD
- IgM
46
High Endothelial Venule (HEV)
- chemokine CCL21 is released from the stromal cells to bring the immature B-cells to the secondary lymphoid tissues then to the primary lymphoid follicles.
- interaction with follicular dendritic cells and cytokines drives maturation of immature B cells
- Mature B-cells will exit the efferent lymphoid and circulate the blood
47
Every B cell will eventually encounter an antigen and be activated for differentiation. This turns B-cells to...
- plasma cells and memory B cells
48
Mature B cells are known as...
- Naive B cells because they havent been stimulate yet
49
Secondary Lymphoid Tissue provides....
- sites where mature, naive B cells can encounter specific antigens
50
Encounter with antigen are quickly retained in the ______ cell areas of the lymph node and become activated by the antigen-specific ________ T- cells
- T
| - CD4
51
Activated B cells turn into....
- plasma cells and secrete IgM first
52
Other activated B cells form ___________ _______ in the lymph node.
- germinal centers (follicle area)
53
Some B-cells chill in germinal centers while other hypermutate to fine tune their antigen specificity. Another word to describe this is...
- somatic hypermutation
54
Germinal centers allow for isotype switching and formation of memory B cells
- mature B cells can encounter antigen in secondary lymphoid tissues and form germinal centers and undergo differentiation to plasma cells
