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VBSC 211: The Immune System > Exam 4: Chapter 6 > Flashcards

Exam 4: Chapter 6 Flashcards

1
Q

How is B cell development regulated?

A

Via checkpoints that occur at the end of each step in B cell development

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2
Q

How are the different stages of B cell development characterized?

A

By distinct sets of surface CD antigens

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3
Q

What occurs in step one of B cell development?

A

The heavy chain rearranges

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4
Q

What occurs in step two of B cell development?

A

The light chain rearranges

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5
Q

In what stage of the B cell does heavy chain D-J rearrangement occur?

A

Early pro-B cell

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6
Q

In what stage of the B cell does heavy chain V-DJ rearrangement occur?

A

Late pro-B cell

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7
Q

In what stage of the B cell does light chain V-J rearrangement occur?

A

Small pre-B cell

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8
Q

In what stage of the B cell is IgM first on the surface?

A

Immature B cell

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9
Q

What cells make up the bone marrow microenvironment?

A

Stromal cells

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10
Q

How do stromal cells regulate B cell development?

A

Stromal cells bind to the developing B cells via adhesion molecule interactions, and stimulate development by producing growth factors and chemokines

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11
Q

What are the two key events in the development of a B cell?

A

The rearrangement of the heavy and light chains

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12
Q

What are productive rearrangements?

A

Heavy and light chain rearrangements that are in frame and produce a working protein

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13
Q

What are unproductive rearrangements?

A

Heavy and light chain rearrangements that are not in frame and/or do not produce a working protein

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14
Q

What happens if the first heavy chain allele fails to form a productive rearrangement?

A

The second heavy chain allele will attempt to produce a productive rearrangement

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15
Q

What happens if both heavy chain alleles fail to form a productive rearrangement?

A

The B cell dies via apoptosis

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16
Q

How many times can each heavy chain allele rearrange?

A

Once

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17
Q

How does a cell test for a productive heavy chain rearrangement?

A

By attempting to bind the heavy chain to the surrogate light chain to form the pre-B cell receptor

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18
Q

What two proteins make up the surrogate light chain?

A

VpreB and lambda-5

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19
Q

What is the role of the Pre-B cell receptor?

A

To signal to the cell that heavy chain rearrangement was successful, thus stopping further heavy chain rearrangement

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20
Q

Is the pre-B cell receptor able to bind antigen?

A

No, because the full binding site is not yet present

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21
Q

How does allelic exclusion apply to heavy chain rearrangement?

A

Only one productive heavy chain rearrangement is allowed to form

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22
Q

How does the B-Cell receptor prevent further heavy chain rearrangement?

A

By sending a signal into the cell that degrades RAG1/2

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23
Q

How would a lack of allelic exclusion affect IgM secretion?

A

IgM would be unable to be secreted as a pentamer due to multiple specificities being present

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24
Q

Where is the heavy chain held while the light chain rearranges?

A

In the Endoplasmic Reticulum

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25
Q

Which light chain rearranges first?

A

The kappa locus

26
Q

How many times can each light chain allele (2 kappa loci and 2 lambda loci) rearrange?

A

As many times as it takes to produce a productive arrangement, or until all combinations have been tried

27
Q

What checkpoint determines if the light chain productively rearranged?

A

Whether or not a full B cell receptor forms on the surface and sends a signal into the cell

28
Q

Must the B cell receptor bind antigen in order to signal that light chain rearrangement is complete?

A

No

29
Q

What would happen if developing B cells could not express lambda-5 or VpreB?

A

B cell development would stop at the pre-B cell stage, because the first checkpoint signal would not be received

30
Q

In addition to productive heavy and light chains, what else does rearrangement produce?

A

Proper arrangements of the promotor and enhancer sequences

31
Q

What are the two types of B cells produced by the body?

A

B1 cells and B2 cells

32
Q

What are the defining qualities of B1 cells?

A

Primarily produced during fetal development; utilize fewer V segments; TdT is not expressed; bind with low affinity; recognize multiple antigens (polyspecificity), recognize polysaccharide and carbohydrate antigens

33
Q

What is the third checkpoint in B cell development?

A

Whether or not the B cell receptor recognizes self antigens

34
Q

What self antigens could potentially be recognized by B cells?

A

Any cell surface protein, glycoproteins, proteoglycans, and glycolipids

35
Q

What happens to B cells that do not react with self antigens?

A

The immature B cells move into the blood stream and begin to express IgM and IgD

36
Q

What happens to B cells that encounter and recognize multivalent antigen on the surface of a bone marrow cell?

A

The B cell receptor becomes crosslinked, sending a strong signal into the B cell that stops development; the B cell must either change its receptor specificity or die

37
Q

What is clonal deletion?

A

The basis of central tolerance; B cells that are auto-reactive and cannot change their specificity die via apoptosis

38
Q

What happens to B cells that encounter and recognize soluble antigens?

A

The B cell enters a state of anergy; the cell migrates into the periphery, but only express IgD; the B cell can no longer be activated

39
Q

What is a tolerance to antigens outside the bone marrow called?

A

Peripheral tolerance

40
Q

What happens to naïve B cells in the periphery?

A

They circulate through the blood and secondary lymphoid organs looking for antigens

41
Q

How do chemokines affect B cells?

A

They guide B cells to the secondary lymphoid organs and promote their interactions with dendritic cells

42
Q

What part of the secondary lymphoid organs do naïve B cells associate with?

A

Primary lymphoid follicles

43
Q

What happens in the primary follicle?

A

Naïve B cells interact with follicular dendritic cells (FDCs), which provide survival signals to the naïve B cells

44
Q

How long do naïve B cells last if they do not interact with FDCs and do not bind antigen?

A

A few days

45
Q

How long do naïve B cells last if they do interact with FDCs, but do not bind antigen?

A

3 to 8 weeks

46
Q

What happens to anergic B cells once they reach the secondary lymphoid organs?

A

They are sequestered in the T cell area and eventually die via apoptosis

47
Q

Where do B cells encounter antigen and become activated into plasma cells?

A

In the secondary lymphoid organs

48
Q

How are antigens brought into the lymph nodes?

A

Via dendritic cells and macrophages

49
Q

What happens when a B cell recognizes antigen in the lymph node?

A

It moves to the T cell area and interacts with CD4+ T cells, which produces signals that induce the B cell to proliferate

50
Q

What are germinal centers?

A

Sites within the lymphoid organs where somatic hypermutation, class switch recombination, and affinity maturation occur

51
Q

What happens to B cells when they differentiate into plasma cells?

A

Switch from B cell receptors on the surface of the cell to secreted antibody via a poly-Adenylation site change

52
Q

How are plasma cells different from B cells?

A

Plasma cells cease to divide, have a limited life span of approx. 4 weeks, no longer express MHC or surface immunoglobulin, and are are unresponsive to further antigen stimulation

53
Q

What are centroblasts?

A

Large proliferating B cells

54
Q

What are centrocytes?

A

Mature centroblasts that have undergone class switch recombination and somatic hypermutation and have been selected by affinity maturation

55
Q

Where do plasma cells develop in the various lymphoid organs?

A

Lymph nodes - medullary cords
Spleen - red pulp
Gut associated lymphoid tissue - lamina propria

56
Q

Why does the germinal center reaction continue on for several weeks?

A

The germinal center produces both plasma cells and memory B cells

57
Q

What are memory B cells?

A

Resting B cells that express high affinity and have isotype switched B cell receptors on their surface

58
Q

What are the properties of memory B cells?

A

Have high affinity B cell receptors, are long lived and do not require restimulation by FDCs, rapidly become plasma cells upon encountering antigen, mainly express IgG

59
Q

What does it mean for B cell tumors to be clonal?

A

They descend from a single cell that was frozen in development

60
Q

What is the High Endothelial Venule?

A

Part of the blood vessel in the lymph node that always expresses the adhesion molecules recognized by B cells

61
Q

Where do B cells develop?

A

In the bone marrow

62
Q

Why are plasma cells generated from germinal centers better than those directly generated by activated B cells?

A

Germinal center plasma cells have the correct Ig isotype and have higher affinity

VBSC 211: The Immune System (10 decks)

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