L6: B Cell Activation

Question 1

What can Abs secreted by plasma cells cause?

Answer 1

• neutraliation: prevents bacterial adherance
• opsonisation: promotes phagocytosis
• complement activation: activates complement which enhances opsonisation and lyses some bacteria

Question 2

B cells only need 1 signal to become activated. True or false?

Answer 2

False, they need several signals

Question 3

How is signal 1 in B cell activation triggered?

Answer 3

By the binding of Ag to BCR in secondary lymphoid tissue

Question 4

What induces intracellular kinases?

Answer 4

BCR-associated polypeptides delivering a specific signal

Question 5

What factors can increase/ decrease signal 1?

Answer 5

• if Ag has activated complement cascade
• lots of C3b
• by complement receptor 2 (CR2) on B cell surface (CD21)
• by CR2/ CD19/ CD81 forming the BCR co receptor complex

Question 6

What affects how B cells recive signal 2?

Answer 6

The type of Ag they bind

- thymus independent (TI) Ag provides signal 2 either by the antigen itself or extensive cross linking of BCR

Question 7

What are the 2 types of Ab production (only IgM) lead by TI Ag?

Answer 7

TI- 1 and TI-2 Ag

Question 8

How do TI- I Ags cause Ab production?

Answer 8

TI- 1 Ag binds BCR and other receptors on B cell providing signal 2

• in [high] these Ag act as polyclonal activators (mitrogens) for B cells, activating many B cells irrespective of their BCR
• the 2 signals (from BCR and TLR) lead to B cell activation, proliferation and absecretion

Question 9

How do TI-2 Ags cause Ab production?

Answer 9

TI-2 Ags contain repeated epitopes and will therefore cross-link many BCR molecules on the same B cell surfaces

• this takes longer (as more Ag required) to induce B cell activation
• Ab responses to TI-2 Ags typically don’t occur until >5yrs in humans

Question 10

What type of cell does TD Ag require the presence of?

Answer 10

CD4+ T cells

Question 11

How are TD Ags able to produce all classes of Abs?

Answer 11

• T cells activated by MHC/ peptide on APC
• BCR binds antigen triggering signal 1
• B cell internalises Ag, processes and presents Ag to CD4+ T cells triggering signal 2 via CD40/ CD40L interaction
• Cytokines secreted by T cell then help B cells to class switch

Question 12

How do B cells ‘act as APC’ for TD Ag?

Answer 12

Epitopes recognised by Ab and T cell must be physically linked, either from different parts of the same molecule or from different molecules of complex

Question 13

*How can B cells ‘acting as APC’ be used to improve the response to TI Ags?

Answer 13

1. B cell binds bacterial polysacc (sugar) epitope linked to tetanus toxid protein
2. Ag internalised and processed
3. Peptides from protein componenet are presented to T cell
4. Activated B cell produces Ab against polysacc Ag on surface of bacterium
   These Abs can now class switch creating a conjugate vaccine

Question 14

What is required for good Ab responses and why?

Answer 14

B/ CD4+ T cell interactions

• B cells enter lymph node from lood and comes into contact with specific Ag and can be activated
• If Ag is TD, B cells present peptide from Ag to CD4+ Th cells are boundary of T/B areas within the lymph node forming B/T cell conjugates

Question 15

What happens as a result of B cells binding Ag via BCR and presenting peptide from Ag to CD4+ Th cell?

Answer 15

T cell then expresses CD40 ligand (CD40L) and secretes cytokines

Question 16

What triggers B cell proliferation?

Answer 16

B cell receives signal 2 from T cell via CD40/ CD40L binding and via cytokine from T cell binding receptors

Question 17

What other molecule can the CD40 signal induce

Answer 17

Activation induced deaminase (AID) which is required for class switching and somatic hypermutation

Question 18

What are germline centres (GCs)

Answer 18

They are centres of increased proliferation formed in the B cell follicle

Question 19

What occurs in GCs?

Answer 19

Cells divide rapidly to become centroblasts and undergo somatic hypermutation of Ig genes and isotype switching

Question 20

When in GCs what are the 3 possible outcomes for B cells?

Answer 20

• differentiate into plasma cell, secreting various isotypes and high affinity Ab somatically mutated
• form long lived memory cells and recirculate
• die within lymphoid tissue

Question 21

What is the main purpose of somatic hypermutation?

Answer 21

It introduces point mutations into V regions of Ig

• there’s ~1 mutation per V region/ cell division
• primarily involves AID and DNA repair genes

Question 22

What other cell type is present in GCs and what is its function?

Answer 22

• Follicular dendritic cells (FDC) which aren’t bone marrow derived.
• They capture intact Ag for centrocytes to bind via BCR
• Oversees B cell affinity maturatino

Question 23

Why do centrocytes compete with each other for Ag on FDC and signals from Tfh cells?

Answer 23

Centrocytes that undergo somatic hypermutation express mutated BCR on surface

Question 24

How can mutated BCR receive a CD40 signal from Tfh cell?

Answer 24

If mutated BCR binds Ag on FDC better than unmutated BCR

Question 25

What are Tfh cells (follicular T helper cells)

Answer 25

They are a CD4+ Th subset mainly found in B cells follicles in lymphocytes.

• specialised to provide help to B cells
• secreted by Th1/2 type cytokines
• can be identified with specific markers that difffers from other subsets of CD4 Th cells

Question 26

How does the CD40 signal turn on somatic hypermutation

Answer 26

Through interactions with Tfh, protecting centrocytes from apoptosis and inducing isotype switching
- different cytokines induce different isotypes to be produced