Lecture 18 - More B Cells Flashcards Preview

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Flashcards in Lecture 18 - More B Cells Deck (32):
1

B cells generated by the liver

B-1 B cells

2

Distinguishing feature of B-1 B cells

Express surface marker CD5
No memory

3

B cells maturing in spleen
1)
a)
b)

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

4

Marginal zone B cell role
1)
2)
3)
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

5

Repertoire of marginal zone B cell BCRs

More limited diversity than other B cell BCR repertoires.

Respond mostly to PAMPS, such as LPS

6

What forms the majority of mature B cells?

Follicular B cells

7

Proportion of B cells that are follicular B cells

~95%

8

Location of follicular B cells

Circulate through the lymph, expressing IgM and IgD

9

Activation threshold of follicular B cells Vs marginal zone B cells

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

10

Antigens that B cells respond to

Protein, polysaccharide, glycoproteins, viral particles, bacteria

11

When does B cell differentiation occur?

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

12

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

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

13

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

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

14

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

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

15

T cell independent B cell activation
1)
2)

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

16

What helps maintain self-tolerance?

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

17

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

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

18

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

Subcapsular sinus

19

Which type of cell is a follicular dendritic cell?

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

20

Chemokine present in paracortical area of a lymph node

CCL21, CCL19

21

Chemokine present in follicle of a lymph node

CXCL13

22

Which receptor detects CCL21 and CCL19?

CCR7

23

Which receptor detects CXCL13?

CXC5R

24

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

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

25

What do germinal centres develop from?

Primary foci

26

What is a primary focus?

A site of B cell proliferation in a lymph node

27

How regularly do B cells divide in a germinal centre?

Every 6-8 hours

28

Growth of germinal centres

Grow in size as immune response progresses
Shrink after ~3-4 weeks

29

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

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

30

Are there many apoptotic B cells in a germinal centre?

Yes. Many

31

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

7-10 days

32

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

Yes, though this is uncommon