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IHL Exam 2 > B Cell activation and development (Bowden) > Flashcards

B Cell activation and development (Bowden) Flashcards

1
Q

Where are the checkpoints in B cell maturation

A

Pre-B cell stage checking 3D arrangement of R
After replacing surrogate light chains
Then negative selection
positive selection

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2
Q

What markers do we use to detect B cells

A

CD19+ and CD20+

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3
Q

How do mature B cells enter tissue

A

HEV

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4
Q

What do resting mature B cells express

A 
BCell R
co-B cell R (CD19, CD81, CR2,) all make CD21
HLA-DR (class II)
CD40
CD45
CD20
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5
Q

B cells that develop from fetal liver-derived stem cells differentiate into what

A

B-1 cells. respond to non-protein Ag in the mucosa (CD5+) GALT and MALT etc

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6
Q

B cells that develop from BM progenitors after both differentiate into what

A

B2 cells

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7
Q

Major subsets of B-2 cells

A

follicular B cells- majority (re-circulating)

Marginal B cells- in spleen and are blood-borne polysaccharide Ags

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8
Q

Antigen dependent overview steps

A

Initiated by Ag(epitope) recognized by B cell R (Idiotope)
Ag binds mIg on naive cells to activate
T dependent or independent manner

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9
Q

Where are naive B cells found

A

secondary lymphoid tissues: primary lymphoid follicles, spleen, and lymph nodes

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10
Q

What cells are found in primary lymphoid follicles

A

Follicular dendritic Cells- not APCs not hematopoietic

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11
Q

Describe the passage through secondary lymphoid tissues

A

enter thru HEV, no antigen yet. migrate to primary follicle, receive signal to survive from FDCs and exit thru lymphatic vessel

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12
Q

What is the bodies mechanism for maintaining concentration of B cells

A

too many B cells, not enough FDCs to provide survival signals
naive B cells die within weeks in absence of antigen

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13
Q

How are B cells “attracted or homing” to tissue location

A

express L-selectin, CCR7, LFA-1 and CXCR4
these bind PNAD, CXCL19, ICAM-1 and CXCR12
chemokine binding activates integrins and follicle migration is mediated by CXCL13

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14
Q

How many signals does B cell activation need

A

2

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15
Q

first signal of B cell activation

A

Ag recognized by mIgM or D- must cross link 2 or more BCR

signal thru Igalpha and beta tails

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16
Q

What is the other version of the first signal for B cell activation

A

Ag binds C3d which is recognized by mIg and CR2(provides the cross linking)
signal thru Ig alpha and beta tails as well as CR2 and CD19 tails

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17
Q

How does lymphocyte migrate after 1st signal of B cell activation

A

B cells down reg CXCR5 and upreg CCR7

T cells down reg CCR7 and upreg CXCR5

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18
Q

What is stimulated when Ag bings the epitope(Ab) in B cell activation

A

degraded, then presented on MHC which when in contact with TCR stimulates B7 expression on B cell

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19
Q

What is the second signal of B cell activation

A

Cd40 on B cell interacts with CD40L on T cell

20
Q

How come CD40L and B7 expression are dependent on antigen stimulation?

A

only lymphocytes interacting with the antigen will be activated= specificity

21
Q

2 general functions of cytokines released by Thelper cells

A 
induce H chain class switching
augment B cell differentiation and proliferation(clonal expansion)
22
Q

Explain the effects of Th cytokines on H chain class switching

A

IL4 promotes IgE
IFNgamma induces IgG2a
TGF-beta and IL5 lead to IgA

23
Q

What is required for HLA isoptope switching? How does this happen?

A

CD40-CD40L so T dependent Ag (proteins only)

Using downstream Constant region(cut out intervening sequences) dependent on cytokines

24
Q

Key enzyme in the HLA isotope switching

A

activation-induced deaminase AID

expressed by CD40

25
Q

What does a naive B cell DNA look like

A

activated VDJ and Cmu and Cdelta, still have all other downstream constant regions

26
Q

Naive cell +LPS DNA

A 
LPS is t independent
no other constant regions are activated aka no class switching
27
Q

Naive cell + LPS and IL4 and soluble CD40L DNA

A

switch area is at IgGgamma and IgE epsilom

28
Q

Naive cell +LPS and TGF-beta DNA

A

IgGgamma2b and Igalpha

29
Q

Class switching depends on how many cytokines

A

all- predominant one wins

30
Q

Somatic hypermutation/affinity maturation

A

Cs–>Us point mutations by AID enzyme in variable region.
expansion or répertoire
want more high affinity Ag specific Ab
T antigen dependent

31
Q

During what stage do Ab increase affinity

A

somatic hypermutation, in germinal centers because interacting with FDC

32
Q

How do mutations change over primary-tertiary response

A

changes start to accumulate at end of primary response, then much more at secondary and tertiary.

33
Q

Plasma cells

A

terminally differentiated B cells.

34
Q

how do we identify plasma cells

A

CD29 secrete super amounts of Ab

35
Q

Memory B cells

A

long periods of time without additional Ag stimulation. Rapid response for future exposure

36
Q

T independent antigens

A

do not require T helper cells. these are mitogens

37
Q

T dependent antigens

A

require T helper cells- contact dependent

38
Q

Do T independent antigen immune responses provide memory cells

A

no

39
Q

What happens in a T dependent Ag response compared to an independent

A

T dependent Ag: have isotope switching, affinity maturation and immunologic memory while TI antigens do not

40
Q

Describe Ab feedback

A

secreted Ab has neg feedback. IgGonly

through Igalpha and beta tails

41
Q

Natural antibodies

A

IgM- produced by B-1 and marginal zone B cells
Specific for local bacteria (limited repertoire)
cross-react with alloantigens

42
Q

What increases when antigen binds naive B cell

A

survival and proliferation
expression of B7
expression of cytokine R like IL2 and IL4 R
expression of CCR7 and migration from follicle to T cell areas

43
Q

When T cells interact with B cell what cascades follow

A

Ab secretion, Isotope switching, affinity maturation and memory B cell production

44
Q

What are the two groups of T-independent antigens and describe

A

TI-1 act as polyclonal stimulators

TI-2 are polymers that activate by cross linking the BCR

45
Q

Most important co stimulatory molecule on B cells

A

CD40- lowers threshold of Ag needed

46
Q

Does class switching the Ig change the specificity of the Ab

A

no, only its isotope– function

IHL Exam 2 (11 decks)

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