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Immunology (Miller) > #3 Anibody Diversity 01.09 > Flashcards

#3 Anibody Diversity 01.09 Flashcards

1
Q

name 3 things that contribute to the diverse B cell repertoire

A
  1. somatic recombination
  2. class switching
  3. affinity maturation aka somatic hypermutation
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2
Q

what is the first step in development of a naive B cell?

A

rearrange Ig genes, i.e., light and heavy chains

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3
Q

what Ig is ALWAYS produced first?

A

pentameric IgM

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4
Q

each Ig molecule produced by any one B cell is ___

A

identical

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5
Q

what is the antibody (Ab) repertoire?

A

the complete collection of Ab/BCR specificities generated by somatic recombination, circulating through the lymphoid tissue

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6
Q

where are B cells made?

A

bone marrow

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7
Q

where does negative selection of B cells occur?

A

bone marrow

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8
Q

where does the B cell precursor rearrange its Ig genes?

A

bone marrow

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9
Q

what is one of the indicators that a B cell is mature?

A

expression of IgD with IgM

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10
Q

what activates a B cell?

A

binding the proper antigen

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11
Q

what do activated B cells give rise to?

A

plasma cells
memory cells
(bone marrow and lymph tissue)

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12
Q

when is a B cell specificity determined?

A

before infection

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13
Q

somatic recombination is antigen ____

A

independent

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14
Q

what 2 enzymes mediate somatic recombination?

A

RAG-1 and RAG-2 (recombination activation genes)

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15
Q

what happens if you are lacking RAG-1 and/or RAG-2?

A

no functional lymphocytes aka B or T cells

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16
Q

what region of the Ig is somatic recombination generating?

A

the variable region of the light and heavy chains

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17
Q

what combines to make the light chain variable region?

A

V+J

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18
Q

what are the two types of light chains?

A

kappa and lambda

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19
Q

can a B cell have both kappa and lambda light chains?

A

no! only one

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20
Q

what is the extra gene segment that heavy chains have as compared to light chains?

A

D

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21
Q

gene segmentation difference between kappa and lambda light chains

A

kappa: all the Js, then a single C
lambda: J and C alternating

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22
Q

what is allelic exclusion?

A

when B cell chain rearrangement occurs, it only happens on one chromosome at a time, otherwise a B cell would express 2 Ab at once

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23
Q

what occurs first, heavy or light chain rearrangement?

A

heavy

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24
Q

what region is changed during class switching?

A

the constant region of the heavy chain

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25
Q

what region is changed during somatic recombinaton?

A

variable region of heavy (VDJ) and light (VJ)

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26
Q

what combines to make the heavy chain variable region?

A

V+D+J

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27
Q

3 things that create diversity of BCR molecules in somatic recombination:

A
  1. V+J or V+D+J giving many different variable regions of light and heavy chains, respectively
  2. the pairing of light and heavy chains
  3. the imprecise joining process of the gene segments (NT that randomly hang on edge)
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28
Q

what is the order of events in somatic recombination of light and heavy chains?

A

somatic recombination (of germline DNA) –> Tx (of the rearranged DNA) –> spicing out of introns (from 1* RNA transcript) –> TL (of RNA) –> polypeptide chain = Ig

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29
Q

order of somatic recombination for the variable region of a heavy chain

A
  1. D+J

2. V+DJ

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30
Q

how many Ab/BCRs are coded for by Ig genes?

A

~10^11

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31
Q

order of Ig heavy chain constant region gene segments ***

A 
Cμ = IgM
Cδ = IgD
Cγ3 = IgG3
Cγ1= IgG1
Cα1 = IgA1
Cγ2 = IgG2
Cγ4 = IgG4
Cε = IgE
Cα2 = IgA2
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32
Q

what is the one Ig gene segment that does not have a preceding switch region?

A

IgD

33
Q

where does recombination occur during class switching?

A

at the switch region

34
Q

what stage of development is the B cell in when it is undergoing class switching? where is its location?

A

B cell is already activated

proliferating in germinal center Rxn

35
Q

what is a terminally class-switched B cell?

A

when a cell and all of its daughter cells will express new Ig/Ab bc all other heavy chain options have been deleted

36
Q

what is the one Ab type that you cannot class switch to?

A

IgD

37
Q

which Ab has no significant secretion?

A

IgD

38
Q

which Ab do you always make first?

A

IgM

39
Q

when a B cell is mature, it expresses…

A

IgM

IgD

40
Q

what is somatic hypermutation/affinity maturation?

A

mutation that occurs at high frequency in the rearranged variable-region DNA of Ig genes in activated B cells

41
Q

what does somatic hypermutation/affinity maturation result in?

A

production of variant Ab

some have higher affinity for antigen

42
Q

in somatic hypermutation, which B cells are positively selected for?

A

those that express higher affinity Ab

43
Q

in somatic hypermutation/affinity maturation, B cells that express ____ affinity for Ab are ____ selected for

A

higher

positively

44
Q

quick-hand version of the constant region of heavy chain

A 
M
D
G3
G1
A1
G2
G4
E
A2
45
Q

three mechanisms for generation of Ab diversity

A
  1. cassette system of gene segments via somatic recombination
  2. class switching
  3. somatic hypermutation/affinty maturation
46
Q

somatic recombination is Ab ____

A

independent

47
Q

class switching is Ab ____

A

dependent

48
Q

somatic hypermutation is Ab ____

A

dependent

49
Q

what changes and what doesn’t change in class switching?

A

changes: the isotype the B cell produces

no change: the antigen specificity

50
Q

what is a critical growth factor that is necessary to mature B cells?

A

IL-7

51
Q

what produces IL-7?

A

stromal cells in bone marrow

52
Q

what stage do B cells begin responding to IL-7?

A

late pro-B cell

53
Q

name the stages of B cell development**

A
  1. stem cell
  2. early pro-B cell
  3. late pro-B cell
  4. large pre-B cell
  5. small pre-B cell
  6. immature B cell
  7. mature B cell
54
Q

B cell development: stem cell

A

germline for both heavy and light chains

55
Q

B cell development: early pro B

A

D-J
begin heavy chain rearranging of variable
region
:: no surface Ig

56
Q

B cell development: late pro B

A

V-DJ
fully rearranged heavy chain variable coding region
:: no surface Ig

57
Q

B cell development: large pre-B cell

A

VDJ

translation of heavy chain

58
Q

B cell development: small pre B

A

V-J

begin light chain rearrangement of variable region

59
Q

B cell development: immature B cell

A

VJ
light chain fully rearranged
begin expressing IgM

60
Q

B cell development:

A

IgD and IgM expressed

61
Q

what can IgD do? what can it not do?

A

can do: bind antigens as well (same affinity) as IgM

can’t: be secreted in significant amounts

62
Q

what is Bruton’s thymidine Kinase (BtK)?**

A

-involved in signal transduction from cell-surface receptors during B cell development

63
Q

what does a lack of Bruton’s thymidine Kinase (BtK) mean?**

A

lack of B cell repertoire

64
Q

what do RAG-1 and RAG-2 (recombination activation genes) do?**

A
  • make double stranded breaks in DNA during somatic recombination
  • critical for rearrangement of B and T cell rearrangement of heavy+light/beta+alpha
65
Q

a lack of RAG-1 and RAG-2 (recombination activation genes) means what?**

A

wont’ have B or T cells / no lymphocytes

66
Q

what is the role of terminal deoxynucleotidyl transferase (TdT)?**

A
  • catalyzes addition of N nucleotides at the junctions between rearranging gene segments of light and heavy chains
  • backfills gaps
67
Q

what is activation-induced cytidine deaminase (AID)?**

A
  • catalyzes switch recombination (class switching)

- required for somatic hypermutation/affinity maturation

68
Q

what would a lack of activation-induced cytidine deaminase (AID) mean?**

A
  • all Ig would be IgM

- very little ability to increase affinity of Ab for antigens in germinal center Rxn

69
Q

where is the immature B cell self-selected for?

A

in the bone marrow

70
Q

if an immature B cell comes into contact with something, what is it most likely?

A

self/host-cell

71
Q

selection of self-tolerant B cells: contact with a multivalent self molecule

A

death/apop in bone marrow

72
Q

selection of self-tolerant B cells: soluble self molecule

A

migrates to periphery

anergic B cell

73
Q

describe an anergic B cell

A

IgD&raquo_space; IgM
:: cannot be activated or respond to stimuli
short life span

74
Q

selection of self-tolerant B cells: low affinity noncrosslinking self molecule

A

migrates to periphery
mature B cell :: IgD and IgM ratio nml
becomes part of repertoire
unclear of self-reactive or not

75
Q

if a B cell is not positively selected for, what happens?

A

it fails to enter the lymphoid follicles

76
Q

if a B cell is positively selected for, what happens?

A

enters lymphoid follicles

stimulation by antigen –> memory B cells, express IgG, IgA, IgE

77
Q

what % of B cells express Ab that have both kappa and lambda light chains?

A

trick question!

0%

78
Q

B cell class switching to IgA can be further signaled to class switching to IgG3. T/F

A

F

Immunology (Miller) (4 decks)

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