Lecture 18 - More B Cells Flashcards
B cells generated by the liver
B-1 B cells
Distinguishing feature of B-1 B cells
Express surface marker CD5
No memory
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
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
Repertoire of marginal zone B cell BCRs
More limited diversity than other B cell BCR repertoires.
Respond mostly to PAMPS, such as LPS
What forms the majority of mature B cells?
Follicular B cells
Proportion of B cells that are follicular B cells
~95%
Location of follicular B cells
Circulate through the lymph, expressing IgM and IgD
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
Antigens that B cells respond to
Protein, polysaccharide, glycoproteins, viral particles, bacteria
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
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
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)
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
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
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
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
Where are the macrophages in a lymph node that pass antigens to follicular DCs located?
Subcapsular sinus
Which type of cell is a follicular dendritic cell?
Not a true dendritic cell
A stromal cell, not from the bone marrow
Non-phagocytic
Chemokine present in paracortical area of a lymph node
CCL21, CCL19
Chemokine present in follicle of a lymph node
CXCL13
Which receptor detects CCL21 and CCL19?
CCR7
Which receptor detects CXCL13?
CXC5R
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
What do germinal centres develop from?
Primary foci
What is a primary focus?
A site of B cell proliferation in a lymph node
How regularly do B cells divide in a germinal centre?
Every 6-8 hours
Growth of germinal centres
Grow in size as immune response progresses
Shrink after ~3-4 weeks
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
Are there many apoptotic B cells in a germinal centre?
Yes. Many
How long does it take for a naive, mature B cell to become a high-affinity plasma cell?
7-10 days
Can a B cell form a memory cell without T cell help?
Yes, though this is uncommon
