B Cells: Development Flashcards

1
Q

phase 1

A

generation of diverse and clonally expressed B-cell receptors in the bone marrow

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2
Q

phase 2

A

alteration, elimination or inactivation of B-cell receptors that bind to components of human body.
*negative selection

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3
Q

phase 3

A

promotion of a fraction of immature B cells to become mature B cells in the secondary lymphoid tissues
* positive selection

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4
Q

phase 4

A

recirculation of mature B cells between lymph, blood, and secondary lymphoid tissues

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5
Q

phase 5

A

activation and clonal expansion of B cells by pathogen-derived antigens in the secondary lymphoid tissues

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6
Q

phase 6

A

differentiation to antibody-secreting plasma cells and memory B cells in secondary lymphoid tissue

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7
Q

are B cells stockpiled?

A

NO, they are constantly replaced
30 billion/day
half life is 50-100 days thus population is winnowed down

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8
Q

when does the D-J of the heavy chain rearrange?

A

Early pro-B cell

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9
Q

when dos the DJ-V of the heavy chain rearrange?

A

Late pro-B cell

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10
Q

what is the first checkpoint of B cell development?

A

after the heavy chain has rearranged

Late pro-B cell

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11
Q

when is the heavy chain made?

A

Large pre-B cell

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12
Q

when does the V-J rearrange of the light chain?

A

small pre-B cell

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13
Q

when is the second checkpoint of B cell maturation?

A

after the light chain has rearranged

small pre-B cell

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14
Q

What is expressed on the surface of an immature B cell?

A

IgM

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15
Q

what is the order of B cell development?

A

early pro, late pro, large pre, small pre, immature

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16
Q

Stromal cells interact and drive B cell development how?

A
  • express adhesion molecules and growth factors
  • B cell receptor expression changes with progression through development
  • Pro-B cells are programmed to die in the absence of survival signals
17
Q

Does the D-J rearrange happen on both chromosomes?

A

yes

*early pro-B cell

18
Q

If the V-DJ doesn’t happen on one chromosome what happens?

A

it gets another chance on the other chromosome, if this also fails then the cell dies. Junctional diversity errors result in non successful formation of heavy chain
*Late pro-B cell

19
Q

Early Pro-B cell

A

RAG proteins activated
heavy chain D and J segments joined
occurs on both chromosomes

20
Q

Late-Pro-B cell

A

heavy V and DJ segments joined
occurs sequentially on chromosomes
two chances for RAR
*first checkpoint happens now for functional heavy chain

21
Q

what is the pre B cell receptor?

causes transition form Pro to Pre B cell

A

it is expressed in the ER
**surrogate light chain expressed and ensures a light chain can bind
Ig alpha and beta expressed(allows signaling)

22
Q

Ig alpha and beta

A

checkpoint clearance
turns of RAG proteins
initiates cell division
-Allelic exclusion(heavy chain only from one chromosome)

23
Q

why is allelic exclusion important?

A

ensures specificity of the heavy chain not allowing for a mixture of heavy chain production

24
Q

Once the late pro-B cell has made it through the checkpoint and transitions into a Large -Pre-B cell what happens?

A

cell division:
100 small pre-B cells
RAG genes activated
unique recombination per cell(light chain)

25
Q

small Pre-B cells light chains are rearranged sequentially how?

A

4-5 recombinations per chromosome
kappa then lambda
-approxiamately 85% of small pre-B cells survive
-Functional antibody expressed on the cell surface (IgM)

26
Q

what are the two checkpoints in B cell developement?

A
  • functional heavy chain(pre B cell receptor) and happens between early and late Pro B-cells
  • functional light chain
  • *both signal through Ig alpha and beta
27
Q

what is negative selection

A

exposure to self antigen and ensures tolerance

  • central tolerance(bone marrow)
  • peripheral tolerance(soluble self antigen)
28
Q

if a B cell binds to self what happens?

A

has a chance to rearrange again, if this fails again then it under goes apoptosis

29
Q

what are the 3 fates negative selection

A
  • light chain reorganization
  • apoptosis
  • anergy(nonfunctional cells)
30
Q

Immature B cells migrate to lymphoid tissues through what?

A

a High endothelial venule (HEV)

31
Q

Where do B cells mature?

A

in secondary lymphoid tissues and reside in the the primary lymphoid follicles

32
Q

what draws immature B cells to secondary lymphoid tissues?

A

CCL 21 and CCL19 released by stromal dendritic cells

33
Q

what does CXCL 13 do?

A

attracts B cells into the primary follicle

34
Q

what drives the maturation of B cells in the primary follicle?

A

interactions with follicular dendritic cells and cytokines via BAFF
**positive selection

35
Q

A mature naive B cell has what expression of IgD and IgM?

A

increased IgD
decreased IgM
*now can circulate in lymph, blood, and secondary tissues

36
Q

Positive selection of B cell

A

lymph node localization

BAFF signaling

37
Q

what are the steps of B cell activation

4 steps

A
  1. antigen exposure in cortex
  2. interaction with T cell (isotype of Ab)
  3. migration to germinal center
  4. plasma cell production and memory cells