B cell maturation and Ab synthesis Flashcards

1
Q

List the steps of B cell maturation

A

Pro-B –> Pre-B —> B cell —> Plasma Cell

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2
Q

During which stage of B cell maturation does D-J rearrangement for heavy chain occur

A

Pro-B cell (early stages of heavy chain production)

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3
Q

During which stage of B cell maturation does V-DJ rearrangement for heavy chain occur?

A

Pre-B cell

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4
Q

Which stage does initiation of light chain rearrangement occur?

A

Pre-B cell to B cell. Once light chain is synthesized, you have a B cell

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5
Q

What stage of B cell maturation secrete antibodies?

A

Plasma cells

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6
Q

Where does differentiation of B-cell occur?

A

in bone marrow

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7
Q

Pre-B cell turns turns on a gene whose product is?

A

Surrogate light chain

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8
Q

Accessory molecule (a fake light chain) that binds to cytoplasmic u heavy chain and brings a small amount to the surface

A

Surrogate light chain

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9
Q

When the surrogate light chain brings a part of the heavy chain to the surface, what two important signals does it give off?

A

Tells cell to stop undergoing further V-DJ rearrangement and to start rearrangement of light chain

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10
Q

Pre-B cell has what marker?

A

Cytoplasmic u heavy chain (recall that IgM is the only Ig present in immature B cell)

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11
Q

Antibody synthesis is mediated by rearrangement of ____ to form functional Ig genes

A

Ig gene segments

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12
Q

First stage of Ab synthesis

A

Rearrangement of heavy chain segments

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13
Q

Heavy chain segments are made of the following gene segments:

A

Variable (V)
Diversity (D)
Joining (J)
Constant Region (C)

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14
Q

VDJ rearrangement results in a functional _____

A

V region

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15
Q

What does the functional V region (VDJ rearrangement) encode?

A

Heavy chain variable domain of the assembled antibody molecule

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16
Q

After VDJ rearrangement, RNA synthesis of the rearranged ehavy chain gene is initiated and proceeds through which region gene segments?

A

C region

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17
Q

What is the primary transcript processed into?

A

mRNA

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18
Q

What is the mRNA then translated into?

A

IgM, D, G, A, or E, depending on the stage of B cell maturation and class switching

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19
Q

Amount of V heavy chain domains (VH)

and V light chains

A

100 VH, 35 VL

20
Q

amount of D heavy chain domains and D light

A

27 DH, and 0 DL!

21
Q

Amount of J heavy chain domains and Jlight

A

6 JH, and 5 JL

22
Q

What is rearranged in light chain?

23
Q

After V-J rearrangement, RNA synthesis of the rarranged light chain gene is initiated and proceeds through the C region gene segments. This primary transcript is processed into what?

24
Q

light chain mRNA is then translated into?

A

Kappa or lambda light chains

25
Once the light chain and heavy chain synthesis have occured, an Ig is assembled where?
In B cell and transported to cell surface
26
When does Ig convert from a membrane anchored form to a secreted form?
Upon differentiation of the B cell into a plasma cell
27
What enzyme mediates the V-DJ rearrangement?
VDJ recombinase; it can cleave/ligate/correct DNA errors
28
VDJ recombinases that are lymphoid specific (T cells and B cells)?
RAG1 and RAG2 = recombinase activating genes (need lymphoid specific so it doesn't occur in...skin or kidney!)
29
What ensures that you have correct rearrangement order of DJ and then V-DJ?
12-23 spacer rule
30
What are the 5 molecule basis of Ig Diversity?
1. Multiple V region genes 2. Recombination of VJ and VDJ gene segments 3. Combinatorial association of H and L chains 4. Junctional Diversity 5. Somatic hypermutation
31
How many multiple V region in heavy and light chains?
V heavy = 100 | V light = 35
32
How many recombination variations can you have for heavy chain VDJ and light chain VJ gene segments?
``` VDJ = 16,200 (100V*27D*6J) VJ = 175 (35V * 5J) ```
33
How many H and L combinatorial associations?
16,200 *175 = 2.836 x 10^6 different combinations
34
When the gene segments come together during the rearrangement process but don't combine faithfully
Junctional diversity
35
This enzyme is shown during VDJ rearrangements in junctional diversity that adds nucleotides in a non-template driven fashion at DNA break points prior to ligation
terminal deoxynucleotidyl transferase
36
Junctional sites on heavy and light chains
heavy chain : V and D, D and J | light chain: V and J
37
When does somatic hypermutation take place?
After B cell engages antigen (antigen dependent)
38
Antibodies mutate at a higher/lower rate than DNA in rest of genome
Higher rate. Particularly in the DNA coding the variable domains
39
What are the two main things Somatic hypermutation contribute to?
1. affinity maturation | 2. upregulates Activation Induced Cytodine Deaminase (AID)
40
higher affinity antibodies will out-compete the lower affinity antibodies (higher affinity B cell will survive, lower affinity dies)
Affinity maturation
41
This enzyme introduces mutations into the variable domains of Igs; contributes to converstions of nucleotides from DNA into RNA (by uridine) leading to affinity maturation
AID
42
When does AID become activated?
When B cell is activated
43
B cells undergo asymmetric division to form?
Memory B cells and plasma cells
44
Circle of DNA consisting of everything between the "D3" and "JH4" connection (could be any one of the Ds with the Js in heavy chain)
Circular episome
45
If you knock out RAG genes, what happens?
Severely compromise immune system
46
2 antigen independent steps of antigen biosynthesis/modification
1. VDJ rearrangement | 2. VJ rearrangemet
47
Antigen dependent steps of antigen production
1. class switching | 2. somatic hypermutation