Pod Test 1, Chapter 4 Development Of B Lymphocytes, Sulentic

Front 1

Describe what happens in phase 1 of B lymphocyte maturation?

Back 1

generation of B cells in the bone marrow

Front 2

Describe what happens in phase 2 of B lymphocyte maturation?

Back 2

elimination of self-reactive B cells in bone marrow

Front 3

Describe what happens in phase 3 of B lymphocyte maturation?

Back 3

activation of B cells by foreign antigen in secondary lymphoid tissues

Front 4

Describe what happens in phase 4 of B lymphocyte maturation?

Back 4

differentiation to antibody-secreting plasma cells and memory B cells in secondary lymphod tissues

Front 5

during which stage does the B cell aquire functional BCRs?

Back 5

phase 1

Front 6

what are the two progeny of a B cell which has been activated by a foreign antigen?

Back 6

1. memory B cell
2. plasma cell

Front 7

what are B cells derived from in the bone marrow?

Back 7

pluripotential hematopoietic stem cells

Front 8

B cell development in the bone marrow is dependent on which non lymphoid cells?

Back 8

stromal cells

Front 9

what are the two functions of stromal cells in regards to B cells?

Back 9

1. the hold them in place in the bone marrow
2. release growth factors that act on B cells

Front 10

what is the growth factor that binds to the immature B cell receptor KIT?

Back 10

stem-cell factor (SCF)

Front 11

which growth factor receptor is displayed on a late pro-B cell that allows it to become a pre-B cell?

Back 11

receptor for interleukin-7

Front 12

what is the first identifiable cell in the B cell lineage?

Back 12

pro-B cell

Front 13

pre-B cells are distinguished by which protein complex on their surfaces?

Back 13

pre-B cell receptor

Front 14

where does DH and JH joining take place?

Back 14

early pre-B cell

Front 15

where does DJH to VH take place?

Back 15

late pre-B cells

Front 16

what is the first type of heavy chain to be produced in B cell receptor development?

Back 16

mu heavy chains

Front 17

describe the light chains of pre-B cells?

Back 17

only have surrogate light chains

Front 18

where are most of the pre-B-cell receptors found in pre-B cells?

Back 18

in the ER

Front 19

once large pre-B cell receptors are produced what happens to the large pre-B cells?

Back 19

the halt rearrangemnet of the heavy chain and proliferate to yeild many small pre-B cells

Front 20

once small pre-B cells are formed describe the events which take place with BCR formation?

Back 20

the pre-B cell receptors are taken apart and mu heavy chains are restricted to cytoplasm while the formation of light chains occurs

Front 21

when the B-cell expresses a fucntional IgM receptor is called what?

Back 21

an immature B cell

Front 22

what is the next step in B cell maturation after the formation of IgM?

Back 22

selection for tolerance of normal body components

Front 23

after tolerance has been established in the immature B cell what is the last developmental aspect before a B cell can be called mature?

Back 23

the formation of IgD on the B-cell surface

Front 24

what is another name for a mature B cell that has not been exposed to antigen?

Back 24

naive B cell

Front 25

where do the most immature B stem cells reside?

Back 25

the subendosteium

Front 26

where do immature B cells become mature B cells?

Back 26

it can occur in either bone marrow or secondary lymphoid organs such as spleen

Front 27

gene rearrangements involving random addition of N and P nucleotides at joints of genes can result in a non-immunoglobulin gene product called a what?

Back 27

unproductive rearrangement

Front 28

rearrangements which give rise to complete and functional immunoglobulins are called?

Back 28

productive rearrangements

Front 29

what is the chance of having a productive rearrangement?

Back 29

1/3

Front 30

what are the immunoglobulin gene loci? (3)

Back 30

1. heavy chain locus
2. kappa light chain locus
3. lambda light chain locus

Front 31

how many copies of immunoglobulin gene loci do B cells have?

Back 31

2, found on homologous chromosomes, one from mom and one from dad

Front 32

what is the importance of being able to rearrange immunoglobulin genes on a B cells maternal and paternal copies?

Back 32

allows for 2 chances instead of one to create a productive rearrangement

Front 33

what happens to a B cell which cannot make a productive rearrangement?

Back 33

it undergoes apoptosis in the bone marrow

Front 34

Review recombination activity of the developing immunoglobulins on B-cells

Back 34

Page 103, Fig 4.7, Parham

Front 35

How do B cells ensure that only one type of heavy and light chain are developed?

Back 35

once a succesful heavy chain or light chain is produced, the protein product of the gene on the cell surface results in a termination signal to DNA recombination

Front 36

which occurs first, heavy chain or light chain development?

Back 36

heavy chain

Front 37

what is the constant region of the surrogate light chain called?

Back 37

lambda 5

Front 38

what is the variable region of the surrogate light chain called?

Back 38

VprepB

Front 39

before binding functional rearranged light chains, mu heavy chains are brought to the cell surface as?

Back 39

dimers with surrogate light chains bound to them

Front 40

what does the tetramer of two mu heavy chains and two surrogate light chains associate with of the cell surface?

Back 40

IgAlpha and IgBeta polypetides

Front 41

After establishing that the mu heavy chains are productive rearrangements what does the pre B cell receptor cause to happen?

Back 41

sends a positive signal to begin mutation on kappa light chains

Front 42

after kappa light chain rearrangement begins what happens to the production of mu heavy chains?

Back 42

it continues, but the heavy chains are kept in the ER and pre B cell receptors are degraded

Front 43

what happens when kappa light chain rearrangment has completed?

Back 43

Same this as heavy chain completion except surrogates are replaced by newly formed kappa light chaines

Front 44

if the kappa light chaines of the IgM are productive, what happens?

Back 44

light-chain rearrangement is shut down

Front 45

what can be said about small pre B cells derived from the same large B cell in regards to heavy and light chains?

Back 45

heavy chains of all small pre B cells are the same, but light chains can potentially be different on all of the small pre B cells

Front 46

what is the enzyme which adds N nucleotides at junctions during rearrangement of gene segments?

Back 46

terminal deoxynucleotidyl transferase (TdT)

Front 47

when is TdT expressed during light and heavy chain formation?

Back 47

only during the rearrangement of heavy chains NOT light chains

Front 48

what phase of B cell development do IgAlpha and IgBeta polypeptides begin to be produced?

Back 48

pro-B cell phase

Front 49

when is IgAlpha and IgBeta polypeptide production halted?

Back 49

after the B cell differentiates into a plasma cell

Front 50

what is a signal transduction molecule that is encoded on the X chromosome and essential for B cell maturation?

Back 50

Bruton's tyrosine kinase (Btk)

Front 51

patients who lack Btk are said to have what immune disorder?

Back 51

X-linked agammaglobulinemia

Front 52

how does X-linked agammaglobulinemia present?

Back 52

constant infections by extracellular bacteria such as Streptococcus pyogenes

Front 53

events that fuse part of one chromosome to another are called?

Back 53

translocations

Front 54

describe the typical translocation of a tumor B cell?

Back 54

immunoglobulin encoding chromosome part is joined with the gene that controls cell growth

Front 55

genes that cause cancer when their function is imparied are called?

Back 55

proto-oncogenes

Front 56

viral genes that can cause a cell to become tumerous are called?

Back 56

oncogenes

Front 57

which proto-oncogene is associated with Burkitt's lymphoma

Back 57

MYC on chromosome 8

Front 58

what is another important proto-oncogene besides MYC that can be involved in B cell tumor formation?

Back 58

BCL12

Front 59

what do B-1 cells express on their cell surfaces that is normally reserved for the human T cell lineage?

Back 59

CD5

Front 60

in addition to CD5, what other surface expression is different that regular (B2) B cells?

Back 60

the express little or no IgD

Front 61

where are B-1 cells most prominent?

Back 61

pleural and peritoneal cavities

Front 62

what is lacking in the rearrangement process of B-1 cells heavy chains that is found in all heavy chains of B-2 cels?

Back 62

N nucleotides because TdT is not present in prenatal period

Front 63

describe the diversity of B-1 vs. B-2 cells?

Back 63

B-2 are more diverse because of the lack of N nucleotide insertion in B-1 cells

Front 64

describe the antibodies secreted by B-1 cells?

Back 64

low affinity, polyspecific (can bind multiple different types of antigen)

Front 65

which antigens are B-1 cells able to make antibodies for?

Back 65

bacterial polysaccharides and other carbohydrate antigens NOT protein antigens

Front 66

When are B-1 cells first produced?

Back 66

fetus

Front 67

When are B-2 cells first produced?

Back 67

postnatal

Front 68

Desceribe the number of N regions in VDL junctions of B-1 cells

Back 68

few

Front 69

Desceribe the number of N regions in VDL junctions of B-2 cells

Back 69

extensive

Front 70

Describe the B-1 cells repertoire?

Back 70

restricted

Front 71

describe the v-region repertoire in B-2 cells

Back 71

diverse

Front 72

what is the primary location of the B-1 cells?

Back 72

peritoneal and pleural cavities

Front 73

what is the primary location of the B-2 cells?

Back 73

secondary lymphoid organs

Front 74

what is the mode of renewel for B-1 cells?

Back 74

self-renewing after birth

Front 75

what is the mode of renewel for B-2 cells?

Back 75

replaced from bone marrow

Front 76

describe the amount sponatneous production of immunoglobulins in B-1 cells?

Back 76

high

Front 77

describe the amount sponatneous production of immunoglobulins in B-2 cells?

Back 77

low

Front 78

describe the amount of IgG as compared to IgM produced by B-1 cells

Back 78

much more IgM

Front 79

describe the amount of IgG as compared to IgM produced by B-1 cells

Back 79

more IgG

Front 80

Do B-1 cells respond to carbohydrate antigen?

Back 80

yes

Front 81

Do B-2 cells respond to carbohydrate antigen?

Back 81

possibly

Front 82

Do B-1 cells respond to protein antigen?

Back 82

possibly

Front 83

Do B-2 cells respond to protein antigen?

Back 83

yes

Front 84

Do B-1 cells require assistance for activation by T cells?

Back 84

no

Front 85

Do B-2 cells require assistance for activation by T cells?

Back 85

yes

Front 86

describe the amount of hyper-mutation in B-1 cells?

Back 86

little to none

Front 87

describe the amount of hyper-mutation in B-2 cells?

Back 87

high

Front 88

describe the amount of memory development in B-1 cells

Back 88

little to none

Front 89

describe the amount of memory development in B-2 cells

Back 89

high

Front 90

how does the production of IgD occur?

Back 90

alternative splicing NOT somatic recombination

Front 91

what is it called when a B-cell binds to liquid self-antigen in the lymph or blood, but does not die or activate?

Back 91

anergy

Front 92

what happens when a B-cell binds an antigen present on a self-cell?

Back 92

its development is arrested

Front 93

what gives the B-cells which bind self-antigens a chance to produce different immunoglobulins?

Back 93

RAG protein synthesis stays high which allows for new light chain production and also halts production of the original light chain that recognized self-antigens

Front 94

continued rearrangement of light chains that recognizes self-antigens is called?

Back 94

receptor editing

Front 95

what is the process called by which B-cells are subject to apoptosis when they cannot form antigens which don't recognize self?

Back 95

clonal deletion

Front 96

where do B-cells congregate in secondary lymphoid tissues?

Back 96

the primary lymphoid follicles

Front 97

what is the specialized stromal cell that is found in the primary lymphoid follicle?

Back 97

follicular dendritic cell

Front 98

what are the large lymphoid follicles of the GALT?

Back 98

Peyers patches

Front 99

in the Peyers patches and other GALT primary lymphoid follicles, what do B-cells become committed to secreting?

Back 99

dimeric IgA

Front 100

why must naive B-cells periodically stop in the primary lymphoid follicles during circulation?

Back 100

the must recieve survival signals to continue to live for further circulation and without these signals B-cells die within a few days

Front 101

what release survival signals in the primary lymphoid follicles?

Back 101

follicular dendritic cells

Front 102

how long does a B-cell which gains entry to a primary lymphoid follicle and recieves survival signals last when it does not bind a antigen?

Back 102

3-8 weeks

Front 103

describe the mechanism by which anergic B-cells are eliminated from circulation?

Back 103

T-cells stop them from entering the primary lymphoid follicles and thus they die without survival signals

Front 104

what happens to B-cells that bind antigen in secondary lymph tissue?

Back 104

T-cells detain these B cells in T-cell areas where they become activated by antigen specific, CD4 helper T cells

Front 105

plasma cells are said to be totally specialized towards what two things?

Back 105

1. constituitive synthesis
2. secretion of antibodies

Front 106

are plasma cells resposive to antigen or interaction with T-cells?

Back 106

no becuase they no longer express surface immunoglobulins or MHC II molecules on the cell surface

Front 107

where do activated B-cells go?

Back 107

primary follicles to start the development of a secondary lymphoid follicle

Front 108

what is the morpholigical difference between a primary and secondary lymphoid follicle?

Back 108

the secondary has a germinal center

Front 109

large proliferating B-cells found in the germinal center are called?

Back 109

centroblasts

Front 110

what do centroblasts mature into?

Back 110

non-dividing centrocytes

Front 111

what is the process called that ensures the centroblast that produces the highest affinity antibodies is selected to produce the centrocytes of the germinal center?

Back 111

affinity maturation

Front 112

what is the essential process in affinity maturation that leads to changes in the affinity of antibodies produced by centroblasts?

Back 112

hyper mutation ??? whats this really called?

Front 113

B cells which survive affinity maturation produce what type of cells in addition to plasma cells?

Back 113

memory B cells which can circulate for long periods of time without entry to the primary lymphoid follicles

Front 114

where do B-cells committed to becoming plasma cells go?

Back 114

medullary cords of lymph nodes, red pulp of spleen, and the lamina propria of gut

Front 115

B cell tumors involving a naive B cell develop where and are called what?

Back 115

develope in follicles of lymph nodes and are called follicular center cell lymphomas

Front 116

B cell tumors involving plasma cells develop where and are called what?

Back 116

develope in bone marrow and are called myelomas

Front 117

what was one of the first tumors to be succesfully treated with radiotherapy and is caused by a mutated germinal center B cell is?

Back 117

Hodgkin's disease