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Immunology > Chapter 6: The Development Of B Lymphocytes > Flashcards

Chapter 6: The Development Of B Lymphocytes Flashcards

1
Q

B cells are important players in…

A
  • adaptive immunity
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2
Q

Stem Cells

A
  • give rise to immune stem cells in bone marrow
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3
Q

Lymphoid Progenitor Cells

A
  • give rise to T and B lymphocytes

- they are the cornerstones of the immune system

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4
Q

B Lymphocytes

A
  • start developing in the bone marrow

- mature B-cells produce specific antibodies against foreign aantigen

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5
Q

T Lymphocytes

A
  • leave bone marrow and migrate to the thymus where they mature
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6
Q

Phase 1 of B cell development

A
  • generation of diverse and clonally expressed B-cell receptors in the bone marrow
  • repertoire assembly
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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
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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
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9
Q

Phase 4 of B-cell development

A
  • recirculation of mature B cells between lymph, blood, and secondary lymphoid tissues
  • Searching for infection
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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
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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
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12
Q

B-cell development is stimulated by…

A
  • bone marrow stromal cells
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13
Q

Stromal cells are needed to…

A
  • provide the microenvironment for the various stages of maturation of hematopoietic stem cells
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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.)
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15
Q

Pro-B cells develop…

A
  • from pluripotent hemapoietic stem cells
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16
Q

Protein Markers on the cell surface…

A
  • identify the cells at their different stages
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17
Q

The different stages in b-cell maturation are correlated with…

A
  • molecular changes that accompany the gene rearrangement
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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

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19
Q

Heavy-chain gene…

A
  • regulates the progression of gene rearrangement (feedback regulation)
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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

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21
Q

Immunoglobulin heavy chain gene rearrangement in pro-b cells give rise to both ___________ and ______________ rearrangements.

A
  • productive

- nonproductive

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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
Q

Even if you could make the heavy chain, you got to get along with the pseudo-light chain (surrogate LC) which are made…

A
  • VpreB and (lambda)5 polypeptides
26
Q

The pre-B receptor is distinguished from the B-cell receptor in that it lacks an immunoglobulin light chain, which is replaced by the ________________________.

A
  • surrogate light chain made up from the VpreB and (lambda)5 polypeptides
27
Q

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.

A
  • remains inside the cell
28
Q

Pre-Be cell receptor causes allelic exclusion

A
  • prevents B cells from making more than one functional heavy (mu) chain
29
Q

Allelic Exclusion at the Ig loci results in B cells w/ antigen receptors of a _______ specificty

A
  • single
30
Q

LC loci rearrangement by small pre-B cell is…

A
  • 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
Q

Pre-B cell events leads to the….

A
  • immature B cell that expresses IgM
32
Q

Development of B cells in Bone Marrow

A
  • 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
Q

Chromosomal translocations

A
  • 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
Q

Burkitt’s Lymphoma

A
  • 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
Q

Which chain genes are rearranged first LC or HC?

A
  • heavy chains are rearranged before LC genes

- HC must develop before the B cell can proceed to the next stage

36
Q

If nonreproductive arrangement is made on one of the chromosome of a homologous pair, then rearrangement is attempted on the second chromosome.

A
  • re read that again
37
Q

Immature B cells can leave the bone marrow…

A
  • 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
Q

Immature B cells w/ specificity for multivalent self antigens are retained in the bone marrow

A
  • NEGATIVE SELECTION
39
Q

Autoreactive modification of B cells

A
  • receptor editing/central tolerance
40
Q

Receptor editing

A
  • 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
Q

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…

A
  • Peripheral tolerance
42
Q

Maturation and survival pf B cells requires access to ____________ _____________.

A
  • lymphoid follicles
43
Q

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?

A
  • undergo positive selection
44
Q

Chemokine attracts them to the ____________ lymphoid tissues.

A
  • secondary
45
Q

They move to the Primary Lymphoid Follicles where they mature and become __________ B-cell and produce a bunch of _________ and fewer ______ on their surfaces.

A
  • Mature
  • IgD
  • IgM
46
Q

High Endothelial Venule (HEV)

A
  • 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
Q

Every B cell will eventually encounter an antigen and be activated for differentiation. This turns B-cells to…

A
  • plasma cells and memory B cells
48
Q

Mature B cells are known as…

A
  • Naive B cells because they havent been stimulate yet
49
Q

Secondary Lymphoid Tissue provides….

A
  • sites where mature, naive B cells can encounter specific antigens
50
Q

Encounter with antigen are quickly retained in the ______ cell areas of the lymph node and become activated by the antigen-specific ________ T- cells

A
  • T

- CD4

51
Q

Activated B cells turn into….

A
  • plasma cells and secrete IgM first
52
Q

Other activated B cells form ___________ _______ in the lymph node.

A
  • germinal centers (follicle area)
53
Q

Some B-cells chill in germinal centers while other hypermutate to fine tune their antigen specificity. Another word to describe this is…

A
  • somatic hypermutation
54
Q

Germinal centers allow for isotype switching and formation of memory B cells

A
  • mature B cells can encounter antigen in secondary lymphoid tissues and form germinal centers and undergo differentiation to plasma cells

Immunology (13 decks)

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