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Host Defense Exam 1 > Antigen Receptor Development > Flashcards

Antigen Receptor Development Flashcards

1
Q

Describe the germline configuration of immunoglobulin gene families.

A
  • there are 3 gene families: kappa light chain, lambda light chain, and heavy chain
  • located on different chromosomes
  • each has a variable region and constant region
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2
Q

What are the segments of the variable region for light chains?

A

V-segments are located at the 5’ end

J-joining segments are located near the 3’end

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3
Q

What are the segments of the variable region for heavy chains?

A

V-segments are located at the 5’end
D-diversity segments are located downstream
J-joining segments are located further downstream near the 3’ end

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4
Q

What do the J and D segments code for?

A

the 3rd CDR on the 3’ end of the antigen binding site

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5
Q

What is the order of gene rearrangement for heavy chains?

A
  1. D-J rearrangement
  2. V-DJ rearrangement
  3. VDJ gene will now be the only V region expressed in that cell
  4. alternative splicing => VDJ-C
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6
Q

What is the order of gene rearrangement for light chains?

A
  1. V-J rearrangement
  2. alternative splicing => VJ-C
  3. kappa or lambda light chain joins heavy chain => IgM
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7
Q

Describe B cell specificity.

A

A single B cell (and its progeny) will only express ONE antigen-binding specificity (1 Vh and 1 VL)

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8
Q

What is allelic exclusion?

A

In Ig-producing cells, only one allele is expressed to ensure antigen specificity

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9
Q

Describe plasma cell specificity.

A

Plasma cells can only make 1 kind of antibody:
1 heavy chain type
1 light chain type
=> B cells may violate this rule (express both IgM and IgD)

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10
Q

List the stages of B cell development.

A
  • HSC
  • pro-B cell (early, late)
  • pre-B cell (large, small)
  • immature B cell
  • mature B cell
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11
Q

Describe gene rearrangement during the HSC stage of B Cell development.

A

all genes are in germline configuration

- no rearrangement occurs

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12
Q

Describe gene rearrangement during the pro-B cell stage of B Cell development.

A
  • D-J rearrangement of the heavy chain (early)

- V-DJ rearrangement of the heavy chain (late)

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13
Q

Describe gene rearrangement during the pre-B cell stage of B Cell development.

A
  • large: now that VDJ gene is produced, mu heavy chain is transiently expressed on the surface, associated with a surrogate light chain (pre-B receptor)
  • small: V-J rearrangement of the light chain
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14
Q

What components make up the pre-B cell receptor?

A

mu heavy chain + surrogate light chain + Ig-alpha + Ig-beta

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15
Q

Which B cell developmental stage is the first time there is Ig expression?

A

pre-B cell large

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16
Q

Describe gene rearrangement during the immature B cell stage of B Cell development.

A

Now that the VJ gene is expressed, the newly produced kappa/lambda light chain will join the mu heavy chain on the surface => IgM on the surface

  • no response to antigens
  • critical control point for gene rearrangement (can no longer make another V region)
17
Q

Describe gene rearrangement during the mature B cell stage of B cell development.

A

immature B cell enters the peripheral lymphoid tissue
begins to express IgD (with the same antigen specificity as IgM)
- responsive to antigens

18
Q

What is the mechanism for Ig gene rearrangement?

A
  1. Recombination Signal Sequence (RSS) is located downstream of V, on both sides of D, and upstream of J.
  2. RAG1/RAG2 recognize the RSS.
  3. RAG loops out the intervening DNA between V/J or J/D
  4. RAG excises the intervening DNA => circularizes => BREC/TREC => deleted
  5. DNA Ligase ligates the ends
19
Q

What is the RSS?

A

RSS is made of 7-9 bps separated by a 12 or 23 bp spacer

- highly conserved

20
Q

What are BRECs/TRECs?

A

B-Cell Recombination Excision Circle

  • excised intervening DNA gets circularized
  • as cell proliferates, the BREC/TREC will get diluted and eventually deleted
21
Q

What is the purpose of quantifying BRECs/TRECs?

A

to see if B cells and T cells are functioning and producing Ig and proliferating

22
Q

How do you get transmembrane IgM vs secreted IgM?

A

alternative splicing of the primary RNA transcript leads to either a transmembrane exon added after the C region or a secretion exon added after the C region

23
Q

How can one cell co-express IgM and IgD?

A
  • primary RNA transcript contains all C-region genes
  • alternative splicing leads to choosing either a Cmu or a Cdelta
  • the VDJ region remains the same, thus conserving antigen specificity
24
Q

What are the 3 mechanisms by which the body increases antibody diversity?

A
  1. Combinatorial Joining of VDJ segments
  2. Junctional Diversity by adding N sequences
  3. Combinations of H and L chain proteins
25
Q

What is combinatorial joining of VDJ segments?

A

every B cell clone expresses a unique VDJ/VJ combination

facilitates increased diversity and antigen specificity

26
Q

What is N-region addition (junctional diversity)?

A
  • After RAG excises the intervening DNA, enzyme Tdt randomly adds nucleotides on the excised ends
  • only occurs in the heavy chain
  • on either end of the DJ segment
27
Q

What is a consequence of N addition?

A
  • nonfunctional antibody due to frameshift or stop/nonsense codon
28
Q

What happens if a B cell receptor is non-functional?

A

apoptosis

29
Q

What are the possible effects of an anti-self B cell receptor?

A

apoptosis, anergy, or receptor editing

30
Q

What is anergy?

A

state of nonfunctionality of B cells that have anti-self receptors that have low autoreactivity

  • decreases IgM expressed on the surface
  • can bind to self proteins, but does not lead to a T cell activity
31
Q

What is receptor editing?

A

If a B cell produces an anti-self receptor, when the Ig binds to a self-antigen a signal is sent to the cell to change the receptor

  • RAG is activated to create a new genetic recombination (since there are still upstream Vs and downstream Js available)
  • this only occurs on the light chain
  • cell continues to mature
  • if still anti-self, apoptosis
32
Q

Describe the structure of T Cell Receptors.

A

2 different chains (alpha and beta)

2 domains each (variable and constant)

33
Q

Which terminal corresponds to which domain of the TCR?

A
  • N domain = variable

- C domain = constant

34
Q

Alpha chains and Beta chains correspond to light or heavy?

A 
alpha = light (VJ)
beta = heavy (VDJ)
35
Q

What is an isotype switch?

A

A B cell can be induced to change the heavy chain it expresses if there are still downstream C regions available
- occurs after B cell is activated and presents to T cells

36
Q

What is the mechanism for an isotype switch?

A
  1. enzyme AID (activation-induce cytidine deaminase) recognizes switch regions upstream of C regions
  2. loop out, excise, ligate
  3. if there are downstream C regions available, you can create a new Ig isotype (with the same antigen specificity)

Host Defense Exam 1 (12 decks)

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