Lecture 5 Flashcards

1
Q

What encodes variable region of heavy chain?

A

V, D, & J genes

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2
Q

What encodes light chain?

A

V & J

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3
Q

How does VDJ gene varry in each cell?

A
  • The organization of theses segments of the genes is the same in EVERY cell in the body EXCEPT the B/T cells in which they are rearranged allowing transcription
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4
Q

What happens in B cell development?

A
  • During B cell development DNA rearrangement must occur in which 1 V segment is placed next to one J segment
  • Everything between the two that are combined is deleted from that B cells genome
  • RNA will then be made, spliced, translated to get us to antibody
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5
Q

Where does VDJ rearrangement occur?

A

Bone marrow

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6
Q

Precursor to B cells?

A

HSC

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7
Q

How many VDJ sements are there?

A

There are ~ 50 - 100 V gene segments
There are ~ 20 - 30 D gene segments
There are ~ 5 - 6 J gene segments

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8
Q

What is purpose of VDJ rearrangement?

A

The creation of a highly specific antibody

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9
Q

What is the order of the rearrangement?

A
  • D if first moved by J then rearranged by V
    All intervening material is deleted
    The rearranged gene will end up close to the constant region
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10
Q

Which antigens drive the rearrangement?

A

This is not antigen driven

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11
Q

What is done in bone marrow transplant?

A
  • Wipe out bone marrow and reconstitute it with HSCs

- CD34 + - the specific HSC that is used in bone marrow transplant

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12
Q

Significance of CD34+

A

HSC used in bone marrow transplant

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13
Q

What is the pro B cell?

A
  • First stage in HSC development: HSC becomes pro B cell
  • VDJ heavy chain rearrangement occurs here
  • Once one allele rearranges, it wants to go to surface of cell so both heavy chains will be same
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14
Q

When does VDJ rearrangement occur?

A

Pro B cell stage

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15
Q

What is the Surrogate light chain?

A
  • Binds to rearranged heavy chain and take it to surface of cell
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16
Q

What happens when heavy chain makes it to surface?

A

Signal sent to cell to stop rearranging so both heavy chains will be the same

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17
Q

What is the the pre B cell?

A
  • What pro B cell becomes
  • Turned off enzyme so heavy change no longer rearranged
  • Enzyme will turn on again to rearrange light chain
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18
Q

What characterizes immature B cell?

A

IgM on surface

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19
Q

What do mature B cells do?

A

Immature B cells leave bone marrow to look for antigens to activate them

20
Q

What is on surface of mature B cells?

A

IgM & IgD

21
Q

What is true of IgM & IgD on matuer B cell?

A
  • Variable region has same specificity

- Differnet antibodies however as constant region is not the same

22
Q

What is allelic exclusion?

A
  • Rearrangement is only occuring on one allele and the other is turning off
  • Prevents one cell from making more than one antibody
23
Q

What does allelic exclusion prevent?

A

B cell from having more than one antibody

24
Q

What is RSS?

A
  • “Recombination signal sequence”

- Conserved sequence found upstream of V and downstream of J

25
Q

What is RAG?

A
  • Recognizes RSS by V & J and cleave sequences between allowing V & J to come together to be ligated
  • The two RSS’s are coming together to ligate to each other
26
Q

What is BREC?

A
  • “B cell recombination excision circle”

- Portion of gene between RRS segments that is cut out

27
Q

How do you tell if bone marrow transplant is taking?

A
  • BRECs will be seen

- Signals that new B cells are being made

28
Q

What is difference between secreted and membrane IgMs?

A
  • The difference is in the C terminal end that will or won’t sit in membrane
  • There will be a secreted or membrane portion on 3’ end of conserved area
29
Q

What determines if Ig is secreted or membrane?

A

Splicing

30
Q

What does IgD do?

A
  • Noone really knows what IgD does, just know it is on surface of mature B cell
31
Q

What is the order of the rearrangement?

A
  • D if first moved by J then rearranged by V
  • All intervening material is deleted
  • The rearranged gene will end up close to the constant region
32
Q

What does IgD do?

A
  • Noone really knows what IgD does, just know it is on surface of mature B cell
33
Q

What is the light chain coded for?

A

Variable region - encoded for by V & J

Constant regoin - C exon

34
Q

How is heavy chain coded for?

A

Variable region - VDJ

Constant region - multiple C exons

35
Q

Where is c regoin found?

A

3’ end of v genes

36
Q

First step in antibody creation?

A

Gene rearrangement

37
Q

What happens after V moved next to DJ?

A

All D segments 5’ of rearrangment are deleted

38
Q

Which cells does VDJ rearrangement occur in?

A

Only those commited to becoming B lymphocytes

39
Q

What is predominant serum Ig?

A

IgG

40
Q

What is predominant secretory Ig?

A

IgA

41
Q

Most B lymphocutes have membrane Ig of what class?

A

IgD

IgM

42
Q

How much more IgM is there in serum than IgE?

A

1000x

43
Q

Antibody fragment with single comining site is designated?

A

Fab

44
Q

Ig classes can be distinguised base on?

A

Their heavy chains

45
Q

First step in rearrangement of heavy chain?

A

D brought next to J and stuff in between has been deleted

46
Q

What is Fab?

A

Variable region