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Immunology > The Life of a B-Cell: Building the Army > Flashcards

The Life of a B-Cell: Building the Army Flashcards

1
Q

What is the general structure of the BCR? What are different ways the formula will be written?

A

Two heavy chains and two light chains, each with variable and constant regions.

H2L2, mu2,kappa2, or mu2lambda2

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2
Q

What features lend to the specificity of the BCR?

How is this acheived?

A

unique VDJh and VJl specific for ONE antigen.

This is achieved by allelic exclusion during the VDJ,VJ recombination stages

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3
Q

What are the four factors that lend to the diversity of B cells?

A
  1. combinatorial diversity- during VDJ rearrangement
  2. junctional diversity- joining sequences are different
  3. N&P nucleotides- noncoding and palindromic nucleotides are added at the junction
  4. Somatic mutation- after the Bcell has specificity for a particular antigen, mutations occur to increase the specificity for the antigen
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4
Q

What three things characterize a memory B-cell?

A
  1. somatic mutation and clonal selection of a particular Fab
  2. Ig heavy chain class switching (IgM to the other types)
  3. rapid response
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5
Q

What is the structure that helps the BCR transmit signal through the B-cell?

A

Iga and Igb (CD79) transmit the signal once a BCR binds and antigen by utilizing ITAMs (immunoreceptor tyrosine-based activation motifs)

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6
Q

What three CD molecules are on the surface of B cells that help them to be identified in clinical and histopath labs?

A

CD19, CD20, CD22

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7
Q

What CD molecule does the pluripotent stem cell use to be self-renewing?

A

CD34

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8
Q

What signal pushes the bone marrow stem cell to develop in the lymphoid lineage?

A

IL-7

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9
Q

What are the four stages of B-cell development?

A

Pro-B
Pre-B
immature B-cell
mature B-cell

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10
Q

What stage of B cell development is the first with B-cell specific markers?

A

Pro-B

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11
Q

What stage of B cell development has a single rearranged BCR heavy chain?

A

Pre-B

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12
Q

What stage of B cell development is the first to express a functional BCR that has not seen an antigen?

A

immature B cell

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13
Q

Where does final B-cell maturation occur?

A

secondary lymphoid organs (spleen, LN)

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14
Q

Where does fetal B-cell development take place?

A

fetal liver

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15
Q

When in the pregnancy do pre-B cells appear?

When in pregnancy does B-cell development switch to the bone marrow?

A

They appear toward the end of the first trimester.

Maturation switches from the liver to the bone marrow in the second trimester

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16
Q

What cellular marker is on over 50% of the newborns B-cells? What are these B cells called?

A

CD5 and the B-cells are called B1 cells (which are T1What -2 independent)

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17
Q

By what age is the B-cell compartment fully functional?

A

2years

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18
Q

In what stages of B-cell development would RAG enzymes be present?

A

Pro-B and Pre-B because these are the enzymes involved in VDJ and VJ rearrangement

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19
Q

In what stage of B-cell development does B-cell tolerance testing occur?

A

Immature B cell because it is testing to make sure the B-cell is not autoreactive.

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20
Q

What Ig’s are expressed on the mature B-cell?

A

mIgD and mIgM

21
Q

What are the three pathways involved in B-cell tolerance?

A
  1. BCR editing
  2. Deletion
  3. Anergy
22
Q

What surface molecules are on the Pro-B cell?

A

CD19- to amplify signal

IL-7R- to differentiate stem cell to lymphoid

23
Q

What surface molecules are on the Pre-B cell?

A

CD19- helps amplify signal
CD79- (like T cells CD3)
CD20 (help develop Bcell to plasma)
IL-7R

24
Q

What surface molecules are on the immature B-cell?

A

CD19, CD20, CD21, CD22
CD79
mIgM

25
Q

What surface molecules are on the mature B cell?

A

mIgM, mIgD
CD19, CD20, CD21, CD22
CD79

26
Q

What are the 2 major event that is occuring during pro-B cell stage?

A
  1. IgH chain is rearranging (D+J and the V+DJ)

2. IL-7 dependent growth is occuring

27
Q

What are the components of the surrogate light chain?

What are the functions of the surrogate LC?

A

VpreB and lambda5

Not polymorphic, helps select B-cells with good BCR heavy chains

28
Q

What is the structure of the BCR in the pre-B stage?

A

The heavy chain is rearranged and there is a surrogate light chain (VpreB and lambda 5) that “holds the place” while the Ig-L is undergoing rearrangement

29
Q

What is the difference between the IgM and IgD expressed on the mature B-cell?

A

They have the same antigen-binding region and VDJ sequence but differ in their constant regions (isotype)

30
Q

What does it mean that the surrogate light chain is non-variant?

A

there is no diversity and it encodes no antigenic specificity

31
Q

What happens if the rearranged heavy chain is structurally sound?

A

It will be in the correct conformation with the surrogate light chain and will elicit a signal via CD79 to allow differentiation to proceed to the next stage (light chain rearrangement)

32
Q

What structure in the TCR is the BCR’s surrogate light chain synonymous to?

A

pTalpha in the pre-TCR which is on DN thymocytes

33
Q

What happens in the pre-B stage if the BCR heavy chain is not structurally sound?

A

RAGs are reactivated to rearrange at the other Ig heavy chain locus

34
Q

What is the other name for B-cell tolerance? What is the mature function of this?

A

negative selection/censoring- to censor self-reactive B cells in the bone marrow before they are released into circulation

35
Q

What stage of B-cell maturation does censoring take place?

Where in the body does it take place?

A

Immature B cell stage in the bone marrow so it can also be called central B-cell tolerance

36
Q

What are the two criteria the B-cell are tested for?

A
  1. productivity- structurally/functionally sound

2. self-reactivity

37
Q

If a B-cell is non-productive, what happens?

A

It goes through BCR editing through secondary VJ rearrangement of the Ig LC locus by reactivating RAG

38
Q

How many attempts does the immature B-cell get for BCR editing before the cell goes through apoptosis or anergy?

A

2-3 times

39
Q

If the immature B-cell is productive and not self-reactive, what is their fate?

A

They continue differentiation to the mature B-cell stage where they acquire IgD and move to the periphery

40
Q

What would force a B-cell to go through apoptosis during negative selection?

A

If the B-cell is strongly reactive to self antigens or are reactive to membrane-bound antigens

41
Q

What is anergy?

What would force B-cells to go through this stage?

A

Functional paralysis of the B-cell if it is weakly reactive to self-antigens or soluble antigens.
It can still exit to the periphery but it has a shorter lifespan

42
Q

What allows the coexpression of IgM and IgD on the mature B-cell?

A

Alternate splicing of the Ig heavy chain RNA that either keeps the mu heavy chain membrane bound transcript or the delta heavy chain membrane bound transcript

43
Q

What sequences are on the mature B cells DNA?

A
  1. productively rearranged VDJ
  2. Cmu with secreted (s) and membrane (m)
  3. Cdelta with secreted (s) and membrane (m) exons
44
Q

Where does central B-cell development occur?
Is it antigen dependent or independent?
What is the product of central B cell development?

A

In the bone marrow and it is antigen independent.

The product is mature B-cells

45
Q

Where does peripheral B-cell development take place?
Is it antigen dependent or independent?
What is the product?

A

In secondary lymphoid organs (LN, spleen)
Antigen dependent
Plasma and memory cells

46
Q

Mutations in Ig-mu, surrogate light chain, or CD79 result in what?

A

Abrogated B-cell development and agammaglobulinemia

The patient lacks B-cells and antibodies

47
Q

What are the two immunophenotyping techniques for B-cell tumors?

A
  1. flow cytometry- can look at expression of molecules on cell, cell size, granularity
  2. immunohistochemistry- staining for Ab against CD20
48
Q

What is B-cell depletion therapy?

A

Retuximab targets CD20 on B cells to deplete b-cell tumors and lymphoma and for rheumatoid arthritis

49
Q

If a drug targeted IL-7, what would occur?

A

The B-cells would not be able to grow or develop so you would have NO B or T cells

Immunology (25 decks)

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