B cell Activation/ Differentiation/ Memory Generation

Question 1

How many types of antigen receptors does each B cell have?

Answer 1

1 single type- many copies

Question 2

What describes how upon stimulation, each B cell creates clones of cells with same antigen receptor?

Answer 2

Clonal selection hypothesis

Question 3

When do B cells make clones?

Answer 3

once activated/ selected for

Question 4

Where does stem cell maturation into immature committed B cells occur?

Answer 4

Bone marrow

Question 5

Where does antigen-dependant proliferation/ differentiation into plasma/ memory cells occur?

Answer 5

Peripheral lymphoid tissue

Question 6

What are B cells that have the BCR but have not encountered antigen called?

Answer 6

Immature B cells

Question 7

What can mature B cells differentiate into?

Answer 7

memory cells
plasma cells (produce antibodies)

Question 8

What are the two B-cell responses?

Answer 8

T-dependant = TD
T-independent = TI

Question 9

What B cell response requires help from T cells?

Answer 9

T-dependent

Question 10

What B cell response does not require T cell help?

Answer 10

T-indipendent

Question 11

What B cell response is typically initiated upon antigen recognition?

Answer 11

T-dependent

Question 12

What B cell response is generated upon exposure to multivalent/ polymerized antigen? (more complex)

Answer 12

T-indipendent

Question 13

How does a TI-1 antigen bind to B cells?

Answer 13

through PRRs/ mlgs (Ig)

Question 14

How does a TI-2 antigen bind to B cells?

Answer 14

cross-link large # of BCRs

Question 15

How many T-independent (TI) forms are there?

Answer 15

2 = TI-1/ TI-2

Question 16

What is the 3-front attack of the T-dependent B-cell response?

Answer 16

1. Directly bind antigen
2. T helper cell binds to/ interacts with B cell
3. TH cell activated- release cytokines/ activate B cell

Question 17

How do B cells bind antigens?

Answer 17

BCR
- initial activation/ proliferation

Question 18

How is some antigen presented on B-cell surface?

Answer 18

some antigen internalized/ processed
- presented on cell surface MHC class II molecules

Question 19

What does TI-1 antigen bind to?

Answer 19

B cells

Question 20

What does TI-2 antigen bind to?

Answer 20

Cd3 complement components
cross-link receptors

Question 21

What receptors is the TI-1 antigen associated with?

Answer 21

Ig and innate
- signalling from both

Question 22

What is CD21?

Answer 22

complement receptor

Question 23

What does a T-dependent antigen require to generate an antibody response?

Answer 23

T-cell help

Question 24

What happens in a T-dependent cell response if you only have B or T cells alone? (mice experiment)

Answer 24

no activation point

Question 25

What are the 3 steps in T-dependent B-cell response?

Answer 25

1. BCR signalling 2. Co-stimulatory interaction/ present antigen to TH cell 3. Cytokine signalling- activate B cell

Question 26

What can individual activated B-cells differentiate into?

Answer 26

- entry to germinal centre - IgM memory cell - plasma cells (secrete antibodies)

Question 27

What part of the lymph node is the B-cell zone?

Answer 27

Follicle

Question 28

What part of the lymph node is the T-cell zone?

Answer 28

Paracortex

Question 29

For the T-dependent B-cell response why is the antigen endocytosed once bound to BCR?

Answer 29

present to T cells

Question 30

What are the 2 ways for an antigen to be endocytosed into B cell?

Answer 30

Lysosomal proteases Actomyosin fibers

Question 31

What cleaves antigen off surface of APC for endocytosis into B cell?

Answer 31

Lysosomal proteases

Question 32

What exerts a pulling force on BCR with a high affinity to bring whole antigen/ APC into B cell? (whole BCR)

Answer 32

Actomyosin fibers

Question 33

What are the 5 steps for BCR antigen endocytosis?

Answer 33

1. Polymerization/ close contact 2. Pull clusters to centre of contact (inc affinity) 3. Initiate uptake 4. Enodyctosis with APC fragments 5. Endocytosis complete

Question 34

What induces internalization (endocytosis of antigen by B cell) and antigen presentation?

Answer 34

Antigen receptor clustering

Question 35

When are BCR-antigen complexes internalized?

Answer 35

endocytosis once signaling begins

Question 36

How are endocytosed antigen fragments presented on B-cell surface to solicit T-cell help?

Answer 36

MHC class II molecules on B cell surface

Question 37

What co-receptors are upregulated by antigen engagement? (B-T cell interaction)

Answer 37

CD40/ CD80/ CD86

Question 38

When are germinal centres formed?

Answer 38

after/ once B cells activated

Question 39

Where are germinal centres in lymph nodes?

Answer 39

inside follicle (B-cell zone)

Question 40

Where in the lymph node is the [ ] of activated B-cells?

Answer 40

germinal centre

Question 41

What are antibody/ Ig-secreting cells?

Answer 41

plasma cells

Question 42

What is the plasma cell fate of a B-cell?

Answer 42

antibody secretion

Question 43

What is the germinal centre fate of a B-cell?

Answer 43

SHM antigen-mediated selection

Question 44

What dictate the fate of antigen-activated B cells?

Answer 44

transcription factors in regulatory network

Question 45

What transcription factor promote germinal centre B cells?

Answer 45

Pax5/ Bcl-6

Question 46

When do Pax-5/ Bcl-6 promote germinal centre B cells?

Answer 46

when coupled with low IRF-4 levels

Question 47

What transcription factor promotes B-cell plasma cell?

Answer 47

BLIMP-1

Question 48

When does BLIMP-1 promote B-cell plasma cells?

Answer 48

when coupled with high IRF-4 levels

Question 49

When during the immune response are plasma cells/ Ig-secreting cells found in lymph node?

Answer 49

first 5-6 days

Question 50

What type of B-cell bears cell surface IgM but does not secrete antibodies?

Answer 50

Naive B-cell

Question 51

What happens when a naive B-cell interacts with an antigen?

Answer 51

becomes plasmablast

Question 52

What are AFCs?

Answer 52

antibody-forming cells = plasmablasts/ plasma cells

Question 53

What are differentiated B-cells that have begun to secrete antibodies but not yet lost capacity to proliferate? - still bear cell surface BCRs

Answer 53

Plasmablasts

Question 54

What prevents free diffusion of lymph fluid into the lymph nodes? (lines the subscapular sinus region)

Answer 54

SCS - control lymph node structure

Question 55

What is the relative lag period of Naive vs Memory B-cells?

Answer 55

Naive- longer Memory- shorter

Question 56

What is the relative time of peak response of Naive vs Memory B-cells?

Answer 56

Naive- longer Memory- shorter

Question 57

What is the relative magnitude of peak antibody response of Naive vs Memory B-cells?

Answer 57

Naive- varies Memory- strong/ specific

Question 58

What antibody isotype is produced by Naive B-cells?

Answer 58

IgM

Question 59

What antibody isotype is produced by Memory B-cells?

Answer 59

IgG/ IgA = class switching

Question 60

What is the relative antibody affinity of Naive vs Memory B-cells?

Answer 60

Naive- low Memory- high

Question 61

What is the relative life span or Naive vs Memory B-cells?

Answer 61

Naive- short Memory- long lived

Question 62

Can naive B-cells recirculate?

Answer 62

yes

Question 63

Can memory B-cells recirculate?

Answer 63

yes

Question 64

What is SHS?

Answer 64

Somatic hypermutation - affinity selection

Question 65

Where does somatic hypermutation occur?

Answer 65

within germinal centre

Question 66

What produces individual point mutations in Ig-heavy and light chain rearrangements? (variability)

Answer 66

SMS

Question 67

What increases the affinity of an antibody for an antigen over time?

Answer 67

AID = activation-induced cytidine deaminase

Question 68

How do SHS point mutations increase?

Answer 68

overtime/ with repeated exposures

Question 69

What followed by affinity selection results in increased affinity for antigen over time?

Answer 69

Mutations (SHM)

Question 70

What is enzyme AID induced by?

Answer 70

Bcl-6

Question 71

What enzyme is responsible for both SHM and CSR?

Answer 71

AID = activation-induced cytidine deaminase

Question 72

What is CSR?

Answer 72

class switching recombination

Question 73

What turns down the expression of DNA damage response genes that might interfere with genetic changes generated during SHM?

Answer 73

AID

Question 74

What happens to B-cells in the germinal centre?

Answer 74

optimation (optimize for future efficient response)

Question 75

What happens to a B-cell when it enters the germinal centre?

Answer 75

proliferation and SHM (somatic hypermutation)

Question 76

What is the traditional antibody isotype produced by naive B-cells?

Answer 76

IgM/ IgD

Question 77

What is the process of expressing any heavy chain class other than IgM/ IgD? (naive ones)

Answer 77

Class switch recombination

Question 78

Where does class switch recombination occur?

Answer 78

germinal centre - after antigen contact

Question 79

What regions does recombination occur between?

Answer 79

donor/ acceptor switch (S) regions

Question 80

What are the donor/ acceptor switch (S) regions?

Answer 80

tandem repeats of short G-rich sequences = 20-80 bp long - contain targeting sites for AID

Question 81

What contains target sequences for AID (enzyme)?

Answer 81

Switch (S) regions - repeats short G-rich sequences

Question 82

What must B cells receive to engage in CSR (class switch recombination)?

Answer 82

costimulatory signals from CD40

Question 83

What determines what isotype is produced in CSR?

Answer 83

which cytokine signal is received

Question 84

What are the different isotypes that can arise in CSR (from IgM/ IgD)?

Answer 84

IgG/ IgE/ IgA

Question 85

What stimulates the transcription of sterile RNAs from germ-line promoters?

Answer 85

Cytokines

Question 86

What is critical to CSR activity?

Answer 86

sterile RNA

Question 87

What would happen if no CD40L in T cells? - costimulatory molecule

Answer 87

not activated- no cytokines produced/ no CSR activity

Question 88

What cytokine signal can produce class switching to IgG or IgE?

Answer 88

IL-4

Question 89

What cytokine signal can produce class switching to IgA or IgG?

Answer 89

TGF

Question 90

What cytokine signal can produce class switching to IgA?

Answer 90

IL-5

Question 91

What cytokine signal can produce class switching to IgG?

Answer 91

IFN-y

Question 92

What T-independent B-cell response is associated with bacterial cell wall components?

Answer 92

TI-1

Question 93

What T-independent B-cell response is associated with capsular polysaccharides?

Answer 93

TI-2

Question 94

What are the 2 subclasses of B-cells that regulate the T-independent antigen response?

Answer 94

B-1 B cells Marginal zone B cells

Question 95

Do T-Independent B cells also go to germinal centre?

Answer 95

no- not same response as T-dependent

Question 96

What B-cell subclass for TI response produces IgM "natural antibodies" that bind broad antigens with low affinity?

Answer 96

BI-1 B cells

Question 97

What B-cell subclass for TI response must receive low-level signals through BCR for survival?

Answer 97

Marginal zone B-cells

Question 98

What B-cell subclass TI is specialized to respond to blood-borne antigen entering immune system through spleen?

Answer 98

Marginal zone B-cells

Question 99

What B-cell subtype can renew themselves in the periphery?

Answer 99

Marginal zone B-cells