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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
What surface molecules are on the mature B cell?
mIgM, mIgD CD19, CD20, CD21, CD22 CD79
26
What are the 2 major event that is occuring during pro-B cell stage?
1. IgH chain is rearranging (D+J and the V+DJ) | 2. IL-7 dependent growth is occuring
27
What are the components of the surrogate light chain? | What are the functions of the surrogate LC?
VpreB and lambda5 Not polymorphic, helps select B-cells with good BCR heavy chains
28
What is the structure of the BCR in the pre-B stage?
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
What is the difference between the IgM and IgD expressed on the mature B-cell?
They have the same antigen-binding region and VDJ sequence but differ in their constant regions (isotype)
30
What does it mean that the surrogate light chain is non-variant?
there is no diversity and it encodes no antigenic specificity
31
What happens if the rearranged heavy chain is structurally sound?
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
What structure in the TCR is the BCR's surrogate light chain synonymous to?
pTalpha in the pre-TCR which is on DN thymocytes
33
What happens in the pre-B stage if the BCR heavy chain is not structurally sound?
RAGs are reactivated to rearrange at the other Ig heavy chain locus
34
What is the other name for B-cell tolerance? What is the mature function of this?
negative selection/censoring- to censor self-reactive B cells in the bone marrow before they are released into circulation
35
What stage of B-cell maturation does censoring take place? | Where in the body does it take place?
Immature B cell stage in the bone marrow so it can also be called central B-cell tolerance
36
What are the two criteria the B-cell are tested for?
1. productivity- structurally/functionally sound | 2. self-reactivity
37
If a B-cell is non-productive, what happens?
It goes through BCR editing through secondary VJ rearrangement of the Ig LC locus by reactivating RAG
38
How many attempts does the immature B-cell get for BCR editing before the cell goes through apoptosis or anergy?
2-3 times
39
If the immature B-cell is productive and not self-reactive, what is their fate?
They continue differentiation to the mature B-cell stage where they acquire IgD and move to the periphery
40
What would force a B-cell to go through apoptosis during negative selection?
If the B-cell is strongly reactive to self antigens or are reactive to membrane-bound antigens
41
What is anergy? | What would force B-cells to go through this stage?
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
What allows the coexpression of IgM and IgD on the mature B-cell?
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
What sequences are on the mature B cells DNA?
1. productively rearranged VDJ 2. Cmu with secreted (s) and membrane (m) 3. Cdelta with secreted (s) and membrane (m) exons
44
Where does central B-cell development occur? Is it antigen dependent or independent? What is the product of central B cell development?
In the bone marrow and it is antigen independent. | The product is mature B-cells
45
Where does peripheral B-cell development take place? Is it antigen dependent or independent? What is the product?
In secondary lymphoid organs (LN, spleen) Antigen dependent Plasma and memory cells
46
Mutations in Ig-mu, surrogate light chain, or CD79 result in what?
Abrogated B-cell development and agammaglobulinemia | The patient lacks B-cells and antibodies
47
What are the two immunophenotyping techniques for B-cell tumors?
1. flow cytometry- can look at expression of molecules on cell, cell size, granularity 2. immunohistochemistry- staining for Ab against CD20
48
What is B-cell depletion therapy?
Retuximab targets CD20 on B cells to deplete b-cell tumors and lymphoma and for rheumatoid arthritis
49
If a drug targeted IL-7, what would occur?
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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