Exam 4: Chapter 6

Question 1

How is B cell development regulated?

Answer 1

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

Question 2

How are the different stages of B cell development characterized?

Answer 2

By distinct sets of surface CD antigens

Question 3

What occurs in step one of B cell development?

Answer 3

The heavy chain rearranges

Question 4

What occurs in step two of B cell development?

Answer 4

The light chain rearranges

Question 5

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

Answer 5

Early pro-B cell

Question 6

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

Answer 6

Late pro-B cell

Question 7

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

Answer 7

Small pre-B cell

Question 8

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

Answer 8

Immature B cell

Question 9

What cells make up the bone marrow microenvironment?

Answer 9

Stromal cells

Question 10

How do stromal cells regulate B cell development?

Answer 10

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

Question 11

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

Answer 11

The rearrangement of the heavy and light chains

Question 12

What are productive rearrangements?

Answer 12

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

Question 13

What are unproductive rearrangements?

Answer 13

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

Question 14

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

Answer 14

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

Question 15

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

Answer 15

The B cell dies via apoptosis

Question 16

How many times can each heavy chain allele rearrange?

Answer 16

Once

Question 17

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

Answer 17

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

Question 18

What two proteins make up the surrogate light chain?

Answer 18

VpreB and lambda-5

Question 19

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

Answer 19

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

Question 20

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

Answer 20

No, because the full binding site is not yet present

Question 21

How does allelic exclusion apply to heavy chain rearrangement?

Answer 21

Only one productive heavy chain rearrangement is allowed to form

Question 22

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

Answer 22

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

Question 23

How would a lack of allelic exclusion affect IgM secretion?

Answer 23

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

Question 24

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

Answer 24

In the Endoplasmic Reticulum

Question 25

Which light chain rearranges first?

Answer 25

The kappa locus

Question 26

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

Answer 26

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

Question 27

What checkpoint determines if the light chain productively rearranged?

Answer 27

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

Question 28

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

Answer 28

No

Question 29

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

Answer 29

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

Question 30

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

Answer 30

Proper arrangements of the promotor and enhancer sequences

Question 31

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

Answer 31

B1 cells and B2 cells

Question 32

What are the defining qualities of B1 cells?

Answer 32

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

Question 33

What is the third checkpoint in B cell development?

Answer 33

Whether or not the B cell receptor recognizes self antigens

Question 34

What self antigens could potentially be recognized by B cells?

Answer 34

Any cell surface protein, glycoproteins, proteoglycans, and glycolipids

Question 35

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

Answer 35

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

Question 36

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

Answer 36

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

Question 37

What is clonal deletion?

Answer 37

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

Question 38

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

Answer 38

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

Question 39

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

Answer 39

Peripheral tolerance

Question 40

What happens to naïve B cells in the periphery?

Answer 40

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

Question 41

How do chemokines affect B cells?

Answer 41

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

Question 42

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

Answer 42

Primary lymphoid follicles

Question 43

What happens in the primary follicle?

Answer 43

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

Question 44

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

Answer 44

A few days

Question 45

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

Answer 45

3 to 8 weeks

Question 46

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

Answer 46

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

Question 47

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

Answer 47

In the secondary lymphoid organs

Question 48

How are antigens brought into the lymph nodes?

Answer 48

Via dendritic cells and macrophages

Question 49

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

Answer 49

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

Question 50

What are germinal centers?

Answer 50

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

Question 51

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

Answer 51

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

Question 52

How are plasma cells different from B cells?

Answer 52

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

Question 53

What are centroblasts?

Answer 53

Large proliferating B cells

Question 54

What are centrocytes?

Answer 54

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

Question 55

Where do plasma cells develop in the various lymphoid organs?

Answer 55

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

Question 56

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

Answer 56

The germinal center produces both plasma cells and memory B cells

Question 57

What are memory B cells?

Answer 57

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

Question 58

What are the properties of memory B cells?

Answer 58

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

Question 59

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

Answer 59

They descend from a single cell that was frozen in development

Question 60

What is the High Endothelial Venule?

Answer 60

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

Question 61

Where do B cells develop?

Answer 61

In the bone marrow

Question 62

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

Answer 62

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