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Immunology > B cell Diversity > Flashcards

B cell Diversity Flashcards

1
Q

Where are B cell first made?

A

Liver of foetus at 8-9 weeks

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2
Q

What variation of light chains are there?

A

Lambda and Kappa

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3
Q

How many constant regions are there in the LC and HC?

A

4-5 in lambda
1 in kappa
9 in HC

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4
Q

Which chain has the D gene segment in B cells?

A

Heavy chain

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5
Q

What happens in heavy chain recombination?

A

DJ recombine first
Then V recombines with DJ

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6
Q

What is needed to recognize antigens?

A

Mostly, HC and LC are required
Exception = some antibodies can recognize with only HC or HL (only 3CDRs needed)
This means it doesn’t matter what the other chain is

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7
Q

What cells do B cell development go through?

A

Haematopoietic stem cells
MPP
CLP
Pre-B
B cell

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8
Q

How do B cell develop?

A

MPP recognize FLT3 ligand with FLT3R
Causes differentiation into CLP
VLA4 binds VCAM1 together with IL-7 commits CLP into early pro-B cell lineage = HC DJ recombination giving a late pro-B cell
V recombining with DJ = pre-B cell
VJ recombination of light chain occur in pre-B cell and Ig expressed intracellularly
Immature B cell has Ig expressed on cell surface

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9
Q

Where is FLT3 ligand found?

A

Bone marrow of stromal cells

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10
Q

What receptor is found in bone marrow stromal cells that CLP binds to?

A

VCAM1 found on the bone marrow stromal cell
It is bound by VLA4

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11
Q

What chain performs repeated rearrangements?

A

Light chain loci

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12
Q

How to eliminate autoreactive B and T cells?

A

T cell = positive and negative selection
B cells = peripheral and central tolerance

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13
Q

Where does central tolerance happen?

A

Bone marrow

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14
Q

What is positive selection and why does this not happen for antibodies?

A

This is selecting for cells that recognize your own MHC
Antibodies don’t need to recognize MHC

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15
Q

What is a mature B cell?

A

Fully VDJ recombined
Light and heavy chain are paired

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16
Q

What happens to immature B cells that have no self reaction? [central tolerance]

A

Migrate to the periphery to become a mature B cell

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17
Q

What happens to immature B cells that have multivalent self reaction? [central tolerance]

A

Clonal deletion or receptor editing
Receptor editing only happens in B cells in the bone marrow

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18
Q

What happens to immature B cells that react to soluble self molecules? [central tolerance]

A

Migrate to the periphery and become anergic B cells

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19
Q

What are anergic B cells?

A

Cells that persist in the periphery but are unresponsive to antigen

20
Q

What happens to immature B cells that have low-affinity to self? [central tolerance]

A

Migrate to periphery to become mature B cell
Clonally ignorant though, don’t bind antigen???

21
Q

What happens in receptor editing?

A

B cell development stops and rearrangement of LIGHT CHAIN

New receptor specificity is not expressed

22
Q

What happens to immature B cells that have no self reaction? [peripheral tolerance]

A

Becomes mature B cells

23
Q

What happens to immature B cells that react to multivalent self molecules? [peripheral tolerance]

A

Apoptosis = NO receptor editing

24
Q

What happens to immature B cells that react to soluble self molecules? [peripheral tolerance]

A

Anergic B cell&raquo_space;> Apoptosis

25
Q

What happens to immature B cells that have low affinity for self? [peripheral tolerance]

A

Become mature B cells = clonally ignorant

26
Q

What does final maturation of B cell occur?

A

When escaped into periphery and passes central and peripheral tolerance = must undergo final maturation step

27
Q

Where does the final maturation step happen?

A

Lymphoid follicles in secondary lymphoid organ
Mostly spleen

28
Q

What are the different types of B cell?

A

Follicular B cell
Marginal zone B cells

29
Q

What signals do they receive?

A

Survival factors = BAFF

30
Q

What cells produce survival factors?

A

Follicular dendritic cells

31
Q

What enzyme initiates somatic hypermutation?

A

AID = activation-induced cytidine deaminase

32
Q

Where is AID expressed?

A

Only in germinal centre B cells

33
Q

What does AID do?

A

Deaminates C into U

34
Q

What repair pathways can be activated to deal with the mismatch?

A

Base excision repair
Mismatch repair
Transcription coupled repair

35
Q

What are the outcomes of somatic hypermutation?

A

Change in affinity, breadth and structural stability of antibodies

36
Q

Where does somatic hypermutation occur?

A

Darkzone of germinal center

37
Q

Where is the germinal centre?

A

In the B cell follicles of secondary lymphoid tissues

38
Q

What role do follicular helper T cells play in B cell somatic hypermutation?

A

B cells mutate their antibody genes in dark zone of germinal centre
B cells w high affinity for antigen can capture and present it w MCH-II
Present it to follicular helper T cells
T cells give survival and mitogenic signals via CD40 and cytokines
B cells that receive help from T cell = can re-enter the dark zone to undergo additional mutation

39
Q

What dictates the Ig Isotypes?

A

The constant region of antibodies = in Fc region

40
Q

What different features do Ig have?

A

Molecular weight, half life, serum level and half-life in serum

41
Q

What is needed for an Ig to be transmembrane?

A

Ig must be hydrophobic = need certain residues

42
Q

Why is dimerization of IgA important?

A

Dimerization is required for transport through epithelial cells

43
Q

When is IgM found as hexamer?

A

In the plasma without J chain

44
Q

What is avidity?

A

Binding strength of entire antibody complex with antigen

45
Q

Describe the affinity in multimeric vs monomeric antibody

A

Binding Kon/Koff = higher for multimeric antibodies

Because more energy is required to remove more antibodies

46
Q
A

Immunology (8 decks)

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