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
Important concept for B and T cell interaction
CD40L ( T cells) and B7 (B cells) are dependent on antigen stimulation only lymphocytes specifically interacting with antigen will be activates **maintains specificity
26
CD40 expression on B cell?
constitutively expressed
27
Class switching in the germinal center
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
cytokine that stimulates IgE production?
IL-4
29
cytokine that stimulates IgG2a production?
IFN-gamma
30
cytokine that stimulates IgA production?
TGF-beta and IL-5
31
what signaling triggers isotype switching?
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
T-dependent antigens?
peptides (proteins only)
33
activation-induced deaminase?
key enzyme in isotype switching | -expressed in response to CD40 signaling
34
Ig in naive B cells
IgM and IgD
35
Ig in naive B cell with LPS
no class switching occurs
36
Ig in naive B cell with LPS and IL-4
switching at gamma and epsilon **keep in mind, will only produce one C region
37
Ig in naive B cell with LPS and TGF-beta
switching at gamma and alpha **keep in mind, will only produce one C region
38
affinity maturation
aka somatic hypermutation under activity of AID -converts Cs to Us introduces point mutations into V regions of gene
39
what is required for affinity maturation?
CD40/CD40L T-dependent antigen required
40
what happens to the selected B cells?
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
TfH
T follicular helper cells
42
do T cell receptors undergo affinity maturation?
NO!
43
over time what happens to the number of somatic mutations?
increases toward end of primary response and with every subsequent exposure (secondary and tertiary response)
44
Plasma Cells
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
CD27
marker for plasma B cells
46
T dependent antigens
require T cell help (contact dependent) proteins specific for the epitope
47
T independent antigens
don't require T cell help bacterial cell wall like LPS activation no memory
48
feedback of B cell response?
**IgG binds the IgG receptor and inhibits antibody production by binding the Ig-alpha and Ig-beta dimers
49
natural antibodies?
IgM produced by B-1 and margin zone B cells specific for bacteria in area cross react with blood alloantigens