Lecture 18 - More B Cells

Question 1

B cells generated by the liver

Answer 1

B-1 B cells

Question 2

Distinguishing feature of B-1 B cells

Answer 2

Express surface marker CD5

No memory

Question 3

B cells maturing in spleen
1)
a)
b)

Answer 3

1) Transitional B-2 B cell differentiates into:
a) Follicular B-2 B cell
b) Marginal Zone B-2 B cell

Question 4

Marginal zone B cell role
1)
2)
3)
4)

Answer 4

1) Embedded in the marginal zone of the spleen, non-circulating
2) Constantly exposed to blood
3) Quickly respond to antigen, have a lower threshold for activation, proliferation and differentiation into antibody-secreting cells
4) Lower affinity, as don’t undergo affinity maturation

Question 5

Repertoire of marginal zone B cell BCRs

Answer 5

More limited diversity than other B cell BCR repertoires.

Respond mostly to PAMPS, such as LPS

Question 6

What forms the majority of mature B cells?

Answer 6

Follicular B cells

Question 7

Proportion of B cells that are follicular B cells

Answer 7

~95%

Question 8

Location of follicular B cells

Answer 8

Circulate through the lymph, expressing IgM and IgD

Question 9

Activation threshold of follicular B cells Vs marginal zone B cells

Answer 9

Follicular B cells have a higher threshold for activation than marginal zone B cells

Question 10

Antigens that B cells respond to

Answer 10

Protein, polysaccharide, glycoproteins, viral particles, bacteria

Question 11

When does B cell differentiation occur?

Answer 11

Differentiation into plasma cells or memory cells occurs after exchange of activation signals with Th cell, during clonal expansion

Question 12

Steps required for co-stimulation
1)
2)
3)

Answer 12

1) Naive T cell must be activated by a dendritic cell presenting antigen (CD80, 86 on DC, CD28 on Th).
2) Activated Th binds mature B cell - TCR binds MHCII/antigen, CD40L binds CD40
3) Th releases IL-4, IL-5, IL-6, IL-21, stimulates B cell

Question 13

Signals required for a naive, mature B cell to be activated
1)
2)

Answer 13

1) Cognate antigen

2) Activation signal (can be T cell dependent or independent)

Question 14

T cell dependent B cell activation
1)
2)
3)

Answer 14

1) B cell BCR encounters cognate antigen, binds it, internalises it
2) Antigen is processed, presented on MHCII
3) Cognate T cell binds to MHCII/antigen complex, provides activation signal to B cell

Question 15

T cell independent B cell activation
1)
2)

Answer 15

1) Repeating cognate epitope, EG: polysaccharide, crosslinks BCR
2) Binding of a PAMP to a PRR (EG: LPS to TLR4) provides activation signal

Question 16

What helps maintain self-tolerance?

Answer 16

Linked activation
Both BCR and TCR need to be cognate for antigen.
Very unlikely that both will be cognate for self antigen

Question 17

How does antigen reach naive B cells?
1)
2)
3)

Answer 17

1) Opsonised antigens enter lymph node, bind to macrophages present in subcapsular sinus
2) Subcapsular macrophages have low endocytic and degradative activity. This preserves antigen on their surfaces, which they present to B cells
3) Antigen is transported to follicle, presented on surface of follicular dendritic cells

Question 18

Where are the macrophages in a lymph node that pass antigens to follicular DCs located?

Answer 18

Subcapsular sinus

Question 19

Which type of cell is a follicular dendritic cell?

Answer 19

Not a true dendritic cell
A stromal cell, not from the bone marrow
Non-phagocytic

Question 20

Chemokine present in paracortical area of a lymph node

Answer 20

CCL21, CCL19

Question 21

Chemokine present in follicle of a lymph node

Answer 21

CXCL13

Question 22

Which receptor detects CCL21 and CCL19?

Answer 22

CCR7

Question 23

Which receptor detects CXCL13?

Answer 23

CXC5R

Question 24

How do B and T cells find one another?
1)
2)
3)
4)
5)
6)

Answer 24

1) When a B cell is activated, it upregulates CCR7
2) This leads it towards the paracortex, where CCL21 is prevalent
3) When a T cell is activated it upregulates CXCR5
4) This leads it towards the follicle, where CXCL13 is prevalent
5) Both B and T cells continue expressing their original surface chemokine receptors, which means they meet t the boundary between the follicle and paracortex
6) If B cell expressing BCR for cognate antigen fails to get T cell help, it dies

Question 25

What do germinal centres develop from?

Answer 25

Primary foci

Question 26

What is a primary focus?

Answer 26

A site of B cell proliferation in a lymph node

Question 27

How regularly do B cells divide in a germinal centre?

Answer 27

Every 6-8 hours

Question 28

Growth of germinal centres

Answer 28

Grow in size as immune response progresses

Shrink after ~3-4 weeks

Question 29

Mechanism of affinity maturation
1)
2)
3)
4)

Answer 29

1) Somatic hypermutation by AID
2) In germinal centre, B cells with higher affinity BCR can more effectively internalise antigen, present it to Th
3) The more a B cell presents to Th, the more proliferative survival signals it receives.
4) If a B cell has a low affinity BCR, it can’t present to Th, doesn’t receive survival signal, undergoes apoptosis

Question 30

Are there many apoptotic B cells in a germinal centre?

Answer 30

Yes. Many

Question 31

How long does it take for a naive, mature B cell to become a high-affinity plasma cell?

Answer 31

7-10 days

Question 32

Can a B cell form a memory cell without T cell help?

Answer 32

Yes, though this is uncommon