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Immunology > Humoral Immunity: B Cell Activation, Affinity... > Flashcards

Humoral Immunity: B Cell Activation, Affinity... Flashcards

1
Q

What are the 2 phases of the B cell life cycle?

A
  1. Antigen independent Phase

2. Antigen dependent phase

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2
Q

How does a B cell life cycle start?

A

B cell starts life as a stem cell and differentiates into a pro-B cell

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3
Q

Describe the first recombination that occurs in the B cell life cycle

A

Undergoes D→ J recombination to join D and J segments (selected randomly) from the gene segment repertoire

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4
Q

What is the second recombination a B cell undergoes?

A

V segment is recombined with DJ segment

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5
Q

What is the role of V(D)J recombination?

A

Hard codes in heavy chain variable region

Expressed with a new constant region to form a heavy chain

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6
Q

What makes a B cell a Pre-B cell?

A

Pro-B cell becomes a pre-B cell when it expresses a heavy chain with a light chain placeholder

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7
Q

How is the light chain of a B cell encoded?

A

Pre-B cell undergoes another round of recombination to join V and J segments of either kappa / lambda chain

Codes in variable and constant light chain regions

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8
Q

What is an immature B cell?

A

B cell becomes immature B cell once expressing heavy and light chain IgM

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9
Q

What mechanisms do B cells undergo to produce variability?

A

Other mechanisms present to introduce variability during V(D)J recombination e.g:

  • Junctional flexibility
  • P and N nucleotide addition
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10
Q

What is the purpose of the variability mechanisms B cells undergo?

A

Generates more diversity even between B cells with the same combination of gene segments

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11
Q

Describe how a mature B cell is formed

A

Mature B cell formed when the B cell is capable of expressing both IgM and IgD through alternative splicing

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12
Q

Where do mature B cells reside?

A

Recirculate between bloodstream, spleen and lymph nodes

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13
Q

When does the antigen-dependent phase of B cell life cycle occur?

A

Occurs after pathogen (virus / bacteria) invades the body

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14
Q

Describe how stem cells differentiate into lymphoid cells

A

As stem cell develops undergoes lymphoid progenitor stem cell differentiation to give rise to B and T cells (which migrate to thymus)

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15
Q

How are T cell receptors formed?

A

T cell have their own TCR generated through similar VDJ recombination processes

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16
Q

What are T helper cells?

A

T helper cells are a subset of T cells involved in B cell activation during infection

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17
Q

Where do activated B cells migrate during antigen-dependent phase?

A

Activated B cells migrate to the GC (germinal centre) where it undergoes affinity maturation

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18
Q

What is the role of affinity maturation process?

A

Affinity maturation improves the affinity of B cells for attacking pathogens

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19
Q

What 3 steps are involved in affinity maturation?

A
  1. Clonal expansion
  2. Somatic hypermutation
  3. Selection
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20
Q

How often does affinity maturation occur?

A

Process is repeated several times until highest possible affinity available

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21
Q

How does class switching occur?

A

Antibodies receive signals to inform them about the pathogens they’re fighting to undergo class switching

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22
Q

What is the purpose of class switching?

A

Class switching enables the presence of appropriate effector functions

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23
Q

What different types do B cells differentiate into after affinity maturation and class switching?

A

Differentiates into plasma cells, secreting antibodies whilst maintaining some BCRs on their surface
A few become memory B cells

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24
Q

Where do the differentiated B cells of the antigen-dependent phase reside?

A

Both memory and plasma B cells circulate in the bloodstream

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25
Q

How are B cells activated?

A

When the body encounters a pathogen, a subset of naive B cells that recognise the pathogen are activated

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26
Q

How many B cells are in the body?

A

More than ~1 billion naive B cells patrol the bloodstream

27
Q

How many B cells are activated when encountered with a pathogen?

A

Only a small portion of the naive cells are activated by the pathogen while the rest remain patrolling

28
Q

What are the 2 stages of B cell activation?

A
  • T-cell independent B cell activation

- T-cell dependent B cell activation

29
Q

What is the first action of B cells once activated?

A

(T-cell independent)

Once activated B cells form clones of themselves (clonal expansion)

30
Q

What are the roles of the B cell clones formed from clonal expansion?

A

Some clones will become first defence (IgM)

Others migrate to lymph node for T cell activation

31
Q

How is B cell activation regulated?

A

Requires triple verification process to ensure the B cells aren’t activated by mistake

32
Q

Outline T-cell dependent B cell activation

A
  1. B cell encounter (BCR) and internalise pathogen
  2. Antigen presented on B cell surface via MHC II receptor
  3. Must be activated by T cell (also activated by same pathogen)
  4. Pathogen engulfed by DC and presented on surface
  5. Th cells detect antigen on DC surface and are activated
  6. B cell activated
  7. CD40-CD40L interaction confirms T helper cell => produces cytokines
  8. Fully activated B cells undergo affinity maturation, class switching and differentiate into plasma cells to secrete antibodies
33
Q

What are the 3 signals required for B cell activation?

A
  • Antigen binding to BCRs
  • Co-stimulation by activated Th cell specific to same antigen
  • Th cell-derived cytokines
34
Q

Summarise B cell activation

A
  1. Differentiation and clonal expansion of activated B cells
  2. 3 signal verification
  3. Signal transduction pathway
35
Q

What are signal transduction pathways?

A

These are complex signal pathways for cell proliferation, differentiation and survival

36
Q

What activates the B cell signal transduction pathways?

A

BCR binding > Activation of tyrosine kinase

37
Q

Outline the signal transduction pathway of B cells

A
  1. Antigen binds to BCR
  2. Tyrosine protein kinases (e.g. SYK)
  3. SYK phosphorylates downstream proteins
38
Q

What is a naive B cell?

A

Naive B cell: Not exposed to antigen yet

39
Q

Which B cells are selected for during affinity maturation?

A

Each B cell has a unique BCR on its surface - BCR that binds the pathogen best is activated

40
Q

How is the best affinity BCR chosen for?

A

The chosen B cell continues cloning itself (clonal expansion) and those clones undergo affinity maturation

41
Q

Describe the initial Ab-antigen affinity

A

When antibody initially generated binds to the antigen it binds at a low-affinity

42
Q

Describe the low affinity antibody-antigen complex

A
  • Antigen takes longer to bind antibody
  • Binds loosely to antibody
  • Quickly detaches after binding
43
Q

How does affinity maturation process mould shape of antibody to better fit the antigen?

A

When B cells activated, affinity maturation process generates mutations in variable region genes to select for genes with highest affinity

Slowly moulds shape of variable region to fit better with the antigen

44
Q

Where does affinity maturation occur?

A

Affinity maturation occurs in the germinal centre of the lymph node

45
Q

What are germinal centres?

A

These are circular cell clusters on the periphery of the lymph node

46
Q

Which 2 types of cell aid with affinity maturation process?

A

Tfh - T follicular helper cells: only T cell that can enter GC

FDCs - Follicular dendritic cells: not normal DCs

47
Q

Where do other T and Th cells reside in lymph node?

A

Other T cells remain in the T cell zone of the lymph node

48
Q

What are the components of the Germinal centre?

A

The germinal centre (GC) is composed of a light and dark zone

49
Q

Which 2 processes occur in the Germinal Centre?

A

2 processes occur in the GC:

  1. Affinity maturation
  2. Class switching
50
Q

When do B cells enter germinal centre?

A

When B cells are activated by Th cells, they migrate into the GC dark zone for clonal expansion

51
Q

What are the stages of affinity maturation?

A

Once cloned B cells undergo affinity maturation: consisting of somatic hypermutation (dark zone) and selection in the light zone

52
Q

Which B cells undergo class switching?

A

The B cell with the highest affinity for the antigen will undergo class switching

53
Q

What do Mature B cells differentiate into?

A

plasma cells or memory B cells

54
Q

What is AID?

A

AID (activation-induced cytidine deaminase)

55
Q

What is the role of AID?

A

Generates point mutations within variable region gene of B cells at random points
(hypermutation)

56
Q

Describe the outcome of somatic hypermutation

A

All B cells that were previously clones now differ from one another

57
Q

When do B cells enter light zone of the germinal centre?

A

Hypermutated B cells enter GC light zone for selection

58
Q

What is the role FDCs in affinity maturation?

A

FDC (follicular dendritic cells) present the antigen on its surface during selection

59
Q

What is the role of Tfh cells in affinity maturation?

A

Tfh cells provide ‘survival’ signal during selection

60
Q

How do hypermutated B cells interact with FDCs and Tfh cells?

A

B cells compete for the limited amount of antigens on the FDC surface and present the antigen to Tfh cells

61
Q

What happens to low affinity B cells during affinity maturation?

A

B cells with low affinity (unable to bind to FDC) undergo apoptosis due to lack of survival signal from Tfh cells

62
Q

What is the result of affinity maturation on high affinity B cells?

A

B cells that survive the process migrate back to dark zone to repeat process until affinity is high enough

63
Q

How does affinity change with each affinity maturation cycle?

A

Ab affinity improves with cycles of affinity maturation

The process is random

Immunology (14 decks)

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