B Cell Development and Activation Flashcards

1
Q

mature naive B cells possess what surface markers?

A
IgM and IgD
Ig-alpha and Ig-beta
CD19 and CD20
CR2
MHC Class I and II
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2
Q

where do mature naive B cells migrate?

A

most to secondary lymphoid organs
-lymph nodes and spleen

enter through HEVs and circulate for weeks

if not activated, die by apoptosis

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3
Q

B-1 cells

A

develop from the fetal liver-derived stem cells
-find in the GALT

respond to non-protein antigen in mucosa

have the CD5 marker**

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4
Q

B-2 cells

A

develop from B cells produced after birth

are follicular and marginal

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5
Q

follicular B cells

A

subset of B-2 cells
**major subset

re-circulating cells (surveillance)

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6
Q

margin B cells

A

subset of B-2 cells
reside in the spleen

don’t recirculate

more likely to respond to blood-borne polysaccharides**

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7
Q

what is necessary for signal transduction of B cells?

A

Ig alpha and beta dimer is necessary

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8
Q

primary lymphoid follicles

A

contain follicular dendritic cells (FDCs)
-present antigen, but not like other APCs

naive B cells interact with the FDCs to be activated

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9
Q

competition for survival signals?

A

not enough FDCs to activate all B cells - those not activated will die

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10
Q

naive B cells express what?

A

L selectin
CCR-7
LFA1
CXCR4

**allow for B cell homing

these surface molecules activate integrins

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11
Q

L selectin

A
on naive B cells
binds Pnad (Peripheral node addressin)
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12
Q

CCR7

A

on naive B cells

binds CXCL19 or CXCL21

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13
Q

LFA1

A

on naive B cells

binds ICAM-1

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14
Q

CXCR4

A

on naive B cells

binds CXC12

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15
Q

CXCL13

A

secreted by FDCs

mediate the follicle migration of naive B cells

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16
Q

What two signals does B cell activation require?

A

antigen recognition by membrane Ig

-must have repeating epitopes

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17
Q

first signal for B cell activation

A

antigen recognition by membrane IgG
-must crosslink 2 or more BCRs

signaling occurs through Ig alpha and beta tails

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18
Q

another way B cells can get first signal?

A

through the B cell co-receptor
pathogen bound with C3d
-binds CR2

-CR2 and CD19 cytoplasmic

results in a 1000x more intense signal

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19
Q

BCR co-receptor complex

A

CD19
CD81
CR2
lg-alpha and Ig-beta

**does not require the crosslinking of membrane bound Ig to initiate response

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20
Q

activated B cells what to alter chemokine receptors?

A

activated in the primary follicle area
downregulate CXCR5 and increase CCR7
-can leave the follicle and go to para-cortex

21
Q

activated T cells what to alter chemokine receptors?

A

in the para-cortex/cortex area
down-regulate CCR7 and increase CXCR5

allows B and T cells to meet and interact

22
Q

second signal of B cell activation

A

two critical ligand pairs

  • B7/CD28
  • CD40/CD40L
23
Q

B7

A

upregulated by stimulation of B cell
-can bind to CD28 on T cells

**first signal of T cell was the TCR MHC class II interaction

allows T cells to perform effector function

24
Q

activation of T cell results in what?

A

increase in expression of CD40L

can interact with CD40 on B cell

provudes signal 2 for the B cell

25
Q

Important concept for B and T cell interaction

A

CD40L ( T cells) and B7 (B cells) are dependent on antigen stimulation

only lymphocytes specifically interacting with antigen will be activates

**maintains specificity

26
Q

CD40 expression on B cell?

A

constitutively expressed

27
Q

Class switching in the germinal center

A

cytokines from T cells provide the switch for this

IL-4 = IgE
IFN-gamma = IgG2a
TGF-beta and IL-5 = IgA

second function is B cell proliferation

28
Q

cytokine that stimulates IgE production?

A

IL-4

29
Q

cytokine that stimulates IgG2a production?

A

IFN-gamma

30
Q

cytokine that stimulates IgA production?

A

TGF-beta and IL-5

31
Q

what signaling triggers isotype switching?

A

CD40:C40L and cytokines

increase the accessibility of the DNA at specific C regions

rearrange VDJ gene segment recombines with a downstream C region (intervening DNA deleted)

32
Q

T-dependent antigens?

A

peptides (proteins only)

33
Q

activation-induced deaminase?

A

key enzyme in isotype switching

-expressed in response to CD40 signaling

34
Q

Ig in naive B cells

A

IgM and IgD

35
Q

Ig in naive B cell with LPS

A

no class switching occurs

36
Q

Ig in naive B cell with LPS and IL-4

A

switching at gamma and epsilon

**keep in mind, will only produce one C region

37
Q

Ig in naive B cell with LPS and TGF-beta

A

switching at gamma and alpha

**keep in mind, will only produce one C region

38
Q

affinity maturation

A

aka somatic hypermutation

under activity of AID
-converts Cs to Us

introduces point mutations into V regions of gene

39
Q

what is required for affinity maturation?

A

CD40/CD40L

T-dependent antigen required

40
Q

what happens to the selected B cells?

A

move back to the germinal center
-B cell now has higher affinity

interacts with FDCs and TfH cells

**only the cells with high affinity antigen receptors are selected to survive

41
Q

TfH

A

T follicular helper cells

42
Q

do T cell receptors undergo affinity maturation?

A

NO!

43
Q

over time what happens to the number of somatic mutations?

A

increases toward end of primary response and with every subsequent exposure (secondary and tertiary response)

44
Q

Plasma Cells

A

terminally differentiated antibody secreting B cells

lose CD19 and 20 expression

identified by CD27**

high secretion rate (hundreds to thousands per second)

survive for long periods of time and capable of mounting the secondary response

45
Q

CD27

A

marker for plasma B cells

46
Q

T dependent antigens

A

require T cell help (contact dependent)

proteins

specific for the epitope

47
Q

T independent antigens

A

don’t require T cell help

bacterial cell wall like LPS activation

no memory

48
Q

feedback of B cell response?

A

**IgG binds the IgG receptor and inhibits antibody production

by binding the Ig-alpha and Ig-beta dimers

49
Q

natural antibodies?

A

IgM

produced by B-1 and margin zone B cells

specific for bacteria in area

cross react with blood alloantigens