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Immunology Block 2 > B Cell Development > Flashcards

B Cell Development Flashcards

1
Q

what are we going to negatively select

A

anything against self will be eliminated

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2
Q

what is positive selection

A

promotion of some immature B cells to become mature b cells in secondary lymphoid tissue

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3
Q

B cell development as fetus happens where

A

fetal liver & bone marrow

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4
Q

once you’re adult where does b cell development happen

A

bone marrow

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5
Q

maturation and positive selection of b cell happen where

A

lymph node, spleen, peyer’s patches

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6
Q

what are central organs (primary)

A

bone marrow and thymus

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7
Q

hematopoietic stem cell is what CD

A

CD34

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8
Q

before you become B cell you make decision that you will be lymphocyte, and what is expressed

A

CD34 and CD10

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9
Q

CLP stands for what

A

common lymphoid progenitor

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10
Q

at immature B cell you have what

A

make u heavy chain and have IgM on surface

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11
Q

What is L chain on large pre-B cell

A

germline

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12
Q

what is L chain on immature B cell

A

VJ rearranged

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13
Q

what is the H chain on large pre-B cell

A

VDJ rearranged

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14
Q

What is H chain on immature B cell

A

VDJ rearranged

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15
Q

what makes pre-b cell a pre-b cell

A

surrogate light chain

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16
Q

what are needed at each stage of maturation

A

cytokines and cell-cell contacts

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17
Q

cell-cell interactions and cytokines regulate what

A

Regulates construction of the BCR
Ensures each B cell has one antigenic specificity
Clonal deletion of self-reactive B cells
Export of mature B cells

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18
Q

SCF stands for

A

stem cell factor

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19
Q

where is SCF expressed

A

stromal cells

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20
Q

SCF has receptor on surface of

A

b cell

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21
Q

what is SCF receptor on surface of b cell

A

Kit

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22
Q

what is the function of Kit-SCF

A

helps b cell survive (early pro-b cell stage)

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23
Q

Late pro-b cell has what signals that helps it continue

A

IL-7: IL-7R

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24
Q

what does IL-7R bind to

A

IL-7

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25
Q

where is IL-7R found

A

on b cell

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26
Q

nonproductive rearangemtn means

A

b cell will die

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27
Q

productive rearrangement means

A

b cell will live, did it right

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28
Q

If V-DJ rearrangment for late pro-B cell doesn’t work what appens

A

try V-DJ rearrangment on the other chromosome

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29
Q

if V-DJ rearrangemnt on the second chrom. you tried doesn’t work for Late pro-B cell what happens

A

death

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30
Q

if V-DJ rearrangement works for late pro-B cell what happens

A

signaled to survive and become pre-B cell

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31
Q

what has surrogate light chain

A

large pre-B cell

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32
Q

which of the following is expressed on surface of an immature B cell

A

IgM

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33
Q

what is expressed on mature B cell

A

IgD and IgM

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34
Q

surrogate light chain has what

A

VpreB and gamma 5

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35
Q

every single pre-b cell will have the same

A

surrogate light chain - it doesn’t vary b/w different light chains

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36
Q

light chain is always

A

different

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37
Q

if you have two different heavy chains what ahppens

A

theywil not bind the same pathogen. they will not be as specific

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38
Q

pts that do not have bruton’s tyrosine kinase

A

no B cells, no immunoglobulin (antibodies)

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39
Q

what does Btk stand for

A

Bruton’s tyrosine kinase

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40
Q

agammglobulinemia means

A

no antibodies in blood

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41
Q

X-linked agammaglobulinemia

A

no b cells and no immunoglobulin

They do not have bruton’s tyrosine kinase

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42
Q

what is the first checkpoint in b cell development

A

use surrogate to see if it can express pre-b cell receptor. if surrogate cannot bind then something is wrong and they induce apoptosis

selection of functional heavy chains

43
Q

selection of functional heavy chain is which checkpoint

A

first

44
Q

if the b cell surives checkpoint and has allelic exclusion what will it do

A

proliferate

45
Q

after b cells proliferate what is re-expressed

A

RAG

46
Q

what does RAG help do to pre-b cell

A

L chain rearrangement

47
Q

for heavy chain it’s harder to get right b/c

A

you are deleting a bunch of space so if you deleted wrong then you don’t have anything to fix it (pg 19)

48
Q

it’s easier to make light chain b/c

A

there are a lot of choices, can try tor lambda, kappa, etc. and if mom’s doesn’t work, then try dad’s. can do this for all of them

49
Q

making L chain doesn’t work what happens

A

die

50
Q

immature b cells will have exactlyt he same

A

h and light chain

51
Q

what is the second checkpoint for b cell development

A

checking for functional light chain

52
Q

some IgM will have antibody sight that is against

A

self

53
Q

immature b cells are tested for what before they can leave bone marrow

A

for autoreactivity - to see if they are going to recognize self

54
Q

what are three mechanisms for negative selection against tolerance to self

A

deletion
anergy
receptor editing

55
Q

negative selection: deletion, describe

A

apoptotic death

56
Q

negative selection: anergy, describe

A

paralysis of function

57
Q

negative selection: receptor editing, describe

A

alteration of specificity

go back to DNA level and edit the V region of the light chain

58
Q

when go back at DNA level for receptor editing what are the choices?

A

edit the V region of the light chain

59
Q

why can’t you go back change heavy chain in DNA

A

you already deleted most stuff, so can’t fix it, it’s gone forever

60
Q

define receptor editing

A

immature B cell binds multivalent self antigen, light chain rearranges for a chance to make BCR with new specificity

61
Q

define clonal deletion

A

immature B cell binds multivalent self antigen leading to apoptosis

62
Q

define clonal anergy

A

immature B cell binds soluble self antigen, becomes paralyzed

63
Q

what is first that happens if you are in bone marrow and stromal cells expressing self antigen and you bind to it

A

this is bad - don’t want to bind to the antigen.

it is retained in bone marrow

64
Q

how can you know b cell is immature

A

no IgD

65
Q

if you do not react with self antigen when you are immature b cell what will happen

A

move to blood and express IgD and IgM and become mature

66
Q

receptor editing, describe in detail what happens

A

go to DNA and edit light chain.
you can edit light chain and use mom or dad allele, still have a lot more choices to try until something works.
get rid of VJ chain we know is bad.
reactivate RAG. get new V and J together and make brand new VJ, hoping the new one will not be against self

67
Q

VJ premade that was sent back by receptor editting is

A

reacting to self - so we don’t want that, want to get rid of it

68
Q

during receptor editing rexpression of what

A

RAG1 & 2

69
Q

once you have edited and chaged light chain from receptor editing, what happens

A

test on self and it doesn’t react, it can go into blood and mature

70
Q

once you have dittied and changed light chain from receptor editing and it reacts to self again what happens

A

it will go back and get editted at DNA level and this keeps happening (to a point) until you get it right

71
Q

when IgM of immature b cell binds to soluble univalent self antigen what happens

A

it is signaled to make IgD and to become unresponsive to antigens (anergic)

72
Q

term for unresponsive b cell

A

anergic

73
Q

once b cell is out of bone marrow and it is in blood where does it go

A

searches for lymph node or other secondary lymph organ

74
Q

in order for b cell to fully develop it needs to go into

A

primary lymphoid follicle

75
Q

HEV stands for

A

high endothelial venules

76
Q

when b cell in HEV there will be what two chemokines

A

CCL21& CCL19

77
Q

what do CCL21 and CCL 19 do

A

attract b cell into lymph node

78
Q

follicular dendritic cells make what chemokine

A

CXCL13

79
Q

CXCL13 does what

A

brings b cell into follicle

80
Q

FDC stands for

A

follicular dendritic cells

81
Q

follicular dendritic cell vs dendritic cell

A

very different, from different precurer, different function

82
Q

follicular dendritic cell mainly found

A

b zone of lymph node

83
Q

the reaction to get into the b zone of lymph node is

A

very compettiive

84
Q

what happens if b cell doesn’t get into b zone of lymph node after it leaves bone marrow

A

it will die :(

85
Q

the majority of b cell is what kind

A

B-2 Cells

86
Q

describe B-2 Cells

A

what we have been talking about, the normal and what most people have
“Conventional B cells” derived from different progenitor cells than B-1 cells
Main players in adaptive humoral responses
Extensive N- and P- nucleotide
Extensive somatic hypermutation

87
Q

B-1 cells are a subpopulation of

A

b cells

88
Q

B-1 cells secrete

A

natural antibody - mostly IgM

89
Q

majority of antigen B-1 cell responds to is

A

polysacharides (sugar!)

90
Q

describe B-1 cells

A

Unique subpopulation of B cells
Extensively studied in mice but recently characterized in humans
Develop prior to birth
Secrete “natural antibody” (mostly IgM)
Little N-nucleotide addition or somatic hypermutation
Broadly antimicrobial - first line of humoral protection

91
Q

are there memory for B-1 cells

A

no

92
Q

B-1 cells are not derived from bone marrow they are

A

self-renewing

93
Q

B-1 cells are first produced

A

fetus

94
Q

b-2 are first produced

A

after birth

95
Q

do b-1 cells require help from t cell

A

no

96
Q

do b-2 cell require help from t-cell

A

yes

97
Q

where is primary location of b-1 cell

A

peritoneal and pleural cavities

98
Q

why don’t b-1 cells need help from t-cell

A

they don’t need help from t-cell b/c t-cell don’t see sugar, they only see linear peptides

99
Q

explain heterogeneous vs. homogenous and allelic exclusion

A

you want the antibody, to have all the chains have the same specificity. that is why you only use mom or only use dad’s dna. if you don’t use allelic exclusion you would have heterogenous and each chain could want to bind to differnt things and it wouldn’t be efficient or effective.
if you use allelic exclusion, you will have only mom or only dad’s, so all the chains will want to bind to the same thing and will be effective.

100
Q

where in the maturation process of b cell can you make mistakes and then have second and third chances to go back and fix

A

Rearrangement of the light-chain loci by pre-B cells is relatively efficient

101
Q

which chain can you go back and fix and have “second chance” to make right

A

light chain

102
Q

successive rearrangments are possible at:

A

Ig light chain loci

103
Q

review and quiz on when proteins are active

A

pg 22

Immunology Block 2 (7 decks)

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